Consistency in the diagnosis of the functional psychoses. A review of the case books of 868 patients who had been admitted into a psychiatric hospital from January 1, 1970, to December 31, 1973, was carried out for consistency in the pattern of diagnosis by the same or different psychiatrists. Of these, 16.5% had a revision in diagnosis. The pertinent literature was reviewed. The possible factors that contribute to the observed inconsistency in diagnosis in this and other investigations are discussed. It is concluded that the problems as reflected in the significant change in diagnosis in this study are multifactorial. It is suggested that these problems may be related to the unknown etiology of the functional psychoses and the absence of identifiable specific lesions.


Primary extranodal lymphoma: response to treatment and factors influencing prognosis. The cumulative 10 year lymphoma experience of a teaching hospital and two of its affiliated institutions was reviewed. From this group, a series of 39 cases of regionally localized primary extranodal lymphomas (Ann Arbor Stages IE and IIE) were selected for study. This group of patients was analyzed for response to initial curative treatment and factors influencing prognosis. The disease-free survival rate following initial treatment is 41% and the rate is 51% if those treated for a single relapse are included. Factors which clearly influence prognosis in this group are stage (extent of disease) at presentation and Rappaport histologic subclassification. The relationships of anatomic site and age to prognosis independent of other factors are unclear. There appears to be an association between sites of involvement in Waldeyer's Ring and the gastrointestinal tract seen both initially and in sites of relapse. An analysis of relapse patterns revealed that 33% of relapses occur as solitary extranodal "skip" recurrences that when treated with radical local treatment may result in long disease-free survival. The latter is one of several findings which suggest that a modification of the current Ann Arbor staging system may be necessary to encompass certain unique features of this group of tumors.


Treatment of malignant ovarian germ cell tumors: response to vincristine, dactinomycin, and cyclophosphamide (preliminary report). From November 1971 to November 1975, 27 patients with malignant germ cell tumors of the ovary (excluding pure dysgerminoma and tumors containing trophoblastic elements) were treated with vincristine, dactinomycin, and cyclophosphamide; 12 patients received other therapy. Fourteen tumors were pure endodermal sinus tumors, two were embryonal carcinomas, 11 were mixed germ cell tumors and 12 were immature teratomas. Of 23 patients with surgically resected disease (Stages I-IIA) only seven have failed. Median follow-up for 16 patients remaining free of disease is 24.5 months. Restaging (second-look) laparotomies were done in 15 patients. Eight were negative. Fifteen of the patients had tumors with endodermal sinus elements. Six of these have failed. Of 16 patients with advanced disease (Stage IIB, III and recurrent), eight have responded to chemotherapy, eight have failed. Median follow-up period for those remaining free of disease is 26.5 months. Six have had negative second-look surgery and one had mature teratoma. Four of eight cases which contained endodermal sinus elements responded to chemotherapy and remain disease-free. Grade 3 hematologic toxicity was seen in eight patients, dose-limiting gastrointestinal toxicity in five patients, dose-limiting neurotoxicity in five patients.


Anatomical substages of stage III Hodgkin's disease: implications for staging, therapy, and experimental design. Twenty-three patients with pathologic stage III Hodgkin's disease were classified with respect to the presence or absence of symptoms (III-A, III-B), the presence or absence of splenic involvement (IIIS+, IIIS-) and anatomic substage--the extent of disease within the abdomen (III1, III2). Stage III1 disease included disease limited to the upper abdomen, i.e., spleen, splenic node, celiac node, and/or portal node. All other more extensive disease was classified as stage III2. Symptoms and splenic involvement did not predict either disease-free survival or survival. However, 5 year actuarial disease-free survival was significantly better in III1 patients as compared to III2 patients (77% vs. 13%, p less than .001). Eight of nine stage III2 patients receiving total nodal radiotherapy alone relapsed. When considered along the previous studies of anatomic substage, these findings suggest that patients in stage III1 and III2 should receive different therapeutic approaches. Analysis of therapeutic results in stage III patients must consider anatomic substage.


Complications of total nodal irradiation of Hodgkin's disease stages III and IV. One hundred twenty-seven patients with Hodgkin's disease, Stages III-IV, received total nodal irradiation. Of these, 101 patients were managed primarily by radiation therapy employing the split course sequential segmental radiation technique called the "3 & 2". A dose of 3800-4000 rad is delivered in 2 phases in an overall period of 12 to 13 weeks (TDF 61-64; 1094-1148 rets). For various reasons, the remaining 26 patients received their mantle irradiation to full doses 3800-4000 rad in 4 weeks (TDF 63-66; 1112-1184 rets) without rest periods and a few were irradiated after failing chemotherapy. Of the 101 patients treated between 1969-1974 using the "3 & 2" technique, 2 developed pericarditis (2.0%), none manifested symptomatic pneumonitis (0%), and 3 hypothyroidism )3.0%). The low incidence of severe complications is primarily the result of the technique employed to give total nodal irradiation. The overall incidence of Herpes Zoster was 42% (53/127), and there was a slightly higher incidence when TNI was given following splenectomy.


A comparative study of the influence of malignant tumor on host metabolism in mice and man: evaluation of an experimental model. Metabolic alterations in skeletal muscles and liver tissue from cancer patients were compared with corresponding alterations in mice (C-57) with sarcoma (MCG-101). In tumor-bearing man and mice similar changes in enzyme activities and in protein turnover were found. Glycolytic and oxidative enzyme activities were decreased in skeletal muscle tissue. Tumor-associated increase in lysosomal enzyme activities was found in both species. Leucine was incorporated into skeletal muscle proteins at a lower rate and into hepatic proteins at a higher rate in both species with malignant tumor. In tumor-bearing mice ribosome profiles from skeletal muscle, heart muscle and liver showed a preponderance of slowly sedimenting units of polyribosomes suggesting that initiation of protein synthesis may be a rate limiting step. The metabolic host reactions in tumor-bearing mice were similar to those in cancer patients implying that experimental tumors are relevant to use for analysis of mechanisms behind the development of cancer cachexia in man.


Histologic findings in the tracheobronchial tree of uranium miners and non-miners with lung cancer. The remaining tissue of the tracheobronchial tree from 210 men who died from lung cancer was studied to compare the histologic alterations leading to further sites of primary cancer. These men were uranium miners matched with nonminers for age and smoking habits. In the examination of a total of 28,928 cross-sections carcinoma in situ was found in 96% of the miners and in 92% of the nonminers. The number of slides from miners showing degree 2 or 3 atypia in areas of carcinoma in situ was about double the number found from the nonminers. Although the difference was not statistically significant, 32% of the miners had at least one section showing early primary invasive carcinoma compared with 22% of the nonminers. The data indicate that the synergistic effect of the exposure to uranium dust along with cigarette smoking increases the risk of lung cancer and that in addition to a main tumor mass, other sites of tissue alterations leading to tumor development are frequently already present in the lung.


Ultrastructure of infantile hemangioendothelioma of the liver. A two-month-old female presented with hepatomegaly 5 cm below the right costal margin. Resection of a 6 cm hepatic mass demonstrated an infantile hemangioendotheliom (IHE). This documents for the first time the ultrastructural features of an IHE of the liver. Ultrastructural examination showed large numbers of vascular channels of varying sizes lined by abnormal endothelial cells. An incomplete basal lamina separated the endothelial cells from the extracellular material and there were no associated pericytes. The intervascular area contained abundant collagen fibers, fibrils, and cells ultrastructurally similar to fibroblasts. The relationship of structure to certain clinical features of this lesion is discussed.


LDH isoenzyme patterns in human gastric mucosa with precancerous changes. By using an original method of electrophoresis separation, the normal relative values of each one of the LDH isoenzymes in the gastric body and antral mucosa were determined. It has been shown in gastric tumors that there is a significance rise in the relative values of "type M" isoenzymes (iso-LDH-4-5). With intestinal metaplasia as well as gastritis, a significant elevation of the relative value of iso-LDH-5 has been demonstrated in the antral mucosa. In 6 benign gastric polyps we found a similar disturbance. This would confirm the known precancerous condition of these lesions. In the normal mucosa of subtotal gastrectomy specimens, 19 patients with antral cancer had 2 types of LDH isoenzyme patterns: one normal and the other with an increase in the relative proportion of "type M" isoenzymes. These LDH isoenzyme pattern shifts in the gastric mucosa could be an early sign of malignancy prior to the morphologic changes.


Human neuroblastoma serially transplanted in nude mice and metastases. A human neuroblastoma from a female patient was directly transplanted into nude mice and serial transplantation was established. Histology of the transplanted tumor was almost the same as that of the patient. During serial transplantation, a high frequency of metastasis to distant organs such as ovaries, lymph node and cerebrum was observed, especially in the ovaries where the metastatic rate reached to 66%. Regarding the distribution of organs involved, there is close similarity between that in the patient with neuroblastoma and tumor-bearing mice. This transplantable human neuroblastoma provided a unique research tool for studies on its morphological and biological nature, including metastasis.


Ultrastructural study of superficial spreading melanoma and benign simulants. Ultrastructural examination of the intraepidermal component of superficial spreading melanomas (SSM) and benign melanocytic lesions was undertaken to determine the diagnostic value of electron microscopy in clinically "borderline" melanoma problems. Seventeen SSMs and ten benign melanocytic nevi and lentigenes which clinically resembled melanoma were studied. Melanocytes of the intraepidermal component of the SSMs showed a greater tendency for abnormal melanosome formation than did melanocytes of the benign simulants. However, the abnormalities were variable and were not limited to the SSMs. Our observations suggest that qualitative ultrastructural evaluation cannot be reliably used differentiating SSMs from benign melanocytic lesions.


Plasma copper and zinc levels in patients with malignant tumors of digestive organs: clinical evaluation of the C1/Zn ratio. The plasma copper level (PCL) and plasma zinc level (PZL) were determined in 126 patients: 54 had carcinomas of which 40 were carcinomas of the digestive organs, 37 had benign lesions, and 35 were without disease. The PCL increased and the PZL decreased significantly in the group with carcinoma of the digestive organs. The CuHZn ratio was not only significantly higher than in the normal group, but also was high in cases with advanced carcinoma especially when liver metastasis was present. Therefore, the Cu/Zn ratio may be valuable in estimating the extent of the carcinoma as well as in determining the prognosis of the cancer patients.


Cystadenocarcinoma and carcinoembryonic antigen (CEA). A 40-year-old woman with back pain, an abdominal and a serum CEA level of 200 ng/ml was found to have at laparotomy, a large but resectable mucinous retroperitoneal mass. Pathologic diagnosis revealed cystadenocarcinoma, probably of pancreatic origin. It is remarkable that the cyst fluid contained a CEA level 100,000-fold normal. Serum CEA fell to normal levels in the postoperative period. This suggests that the CEA was of cyst epithelial origin.


Characteristics of adenocarcinomas of the colorectum with low levels of preoperative plasma carcinoembryonic antigen (CEA). Carcinoembryonic antigen (CEA) is evaluated preoperatively and then serially postoperatively in 97 patients with colorectal carcinoma. CEA is initially elevated (greater than 2.5 ng/ml) only in 58% of the these patients. The group without preoperative CEA elevation has a statistically significant higher proporation of Dukes A lesions (p less than 0.05), seems less likely to suffer recurrence or have CEA elevation at the time of recurrence, and has a longer disease-free interval, than the group with preoperative CEA elevation. However, no distinction between the two groups can be made on the basis of the patients age, sex, presenting signs and symptoms, or location and size of their primary lesions. Higher postoperative CEA values are associated with liver metastases in both groups.


Immunoblastic sarcoma of the central nervous system in a patient with lymphomatoid granulomatosis. A 26-year-old man with lymphomatoid granulomatosis (LYG) was found at postmortem examination to have an immunoblastic sarcoma involving the central nervous system. Residual evidence of LYG was present only in the lungs at autopsy. Studies for intracellular immunoglobulin utilizing the immunoperoxidase technique showed a marked polyclonal reaction in sections of lymph nodes and occasional cells in the cellular central nervous system tumor that stained for intracellular immunoglobulins (IgG, IgM and both kappa and lambda). This case may represent another example of immunoblastic sarcoma occurring in the presence of an abnormal immune state or proliferation.


Acinic cell adenocarcinoma of minor salivary glands. Nine cases identified as acinic cell adenocarcinoma of minor salivary glands from the files of the Armed Forces Institute of Pathology and the Department of Pathology, Temple University School of Dentistry were studied to determine the clinical and histomorphologic parameters of this lesion. One case was examined ultrastructurally. Clinical results show that the tumor is more common in females and the average age of patients was 42.5 years. The most common sites were upper and lower lips and buccal mucosa. The tumor tends to be locally limited, but recurrence is a distinct possibilty. Cytologic features usually associated with malignancies are generally not present. However, perineural space and muscle invasion occur, and it is felt that this tumor should be considered as a low-grade malignancy. Fine structural observations showed the presence of cells with serous secretory granules and cells with mucous globules. However, the serous secretory granules were not as numerous as those reported in the acinic cell adenocarcinoma of the parotid gland. It appears that these tumors arise from intercalated duct cells or pluripotential duct cells rather than from fully differentiated serous cells.


Malignant apudoma of the liver with symptomatic intractable hypoglycemia. This report documents a case of a fatal primary malignant neoplasm of the liver with metastases to the lymph nodes of the porta hepatis and the pubic bone. Profound, intractable hypoglycemia was seen during the course of the disease. No immunoassayable insulin was found in the blood during episodes of severe, symptomatic hypoglycemia. The neoplasm was composed of uniform polygonal cells with distinct cytoplasmic borders growing in broad strands with a tendency toward nesting and was morphologically similar to neoplasms of neural crest derivation. The presence of osmophilic, membrane-bound granules in the neoplastic cells was documented by ultrastructural studies. The tentative conclusion that the hypoglycemia was produced by the secretion of a substance with insulin-like activity, probably a polypeptide, by the secretory granules in the neoplastic cells is supported by clinical and laboratory data.


Thin needle biopsy in the diagnosis of ureteral obstruction with malignancy. Ureteral obstruction after treatment for abdominal cancers is a common situation in which the thin needle biopsy presents an attractive low morbidity alternative to laparotomy for the diagnosis of malignant disease. A negative biopsy is still nonconclusive, although helpful in determining the next step in the patient's management. In our own series, biopsy in the region of ureteral obstruction revealed tumor rather than benign disease in four of five patients. No morbidity was encountered.


Liposarcoma of the neck: a clinicopathologic study of 4 cases. A clinicopathological study of 4 patients with liposarcoma in the neck treated surgically is presented. Three of the liposarcomas were located in the supraclavicular region, two to the right one to the left, and one appeared to the left in the back of the neck. Liposarcoma rarely involves the head and neck region. A survey is given of the few reported liposarcomas in this region. Two of the tumors in the present series were well differentiated, one of which recurred repeatedly. The other two tumors were round-cell and pleomorphic in type, both of which recurred. At the end of follow-up 11 and 9 years, the two patients with well-differentiated liposarcomas were alive. The other two patients had died after 5 and 4 years from intercurrent disease and metastatic spread, respectively. The histopathological basis for the diagnosis, distinguishing features of intramuscular (infiltrating) lipoma, hibernoma and spindle cell lipoma, as well as the treatment, are discussed.


A simple technique for increasing cancer patients knowledge of informed consent to treatment. Seventy-seven sequential patients referred to a radiation oncology clinic for treatment of malignant neoplasms were tested for their immediate recall of information presented, recorded, and signed on informed consent documents. An experimental group of 40 patients were given the intervention of taking the completed form home before signing. Results support the usefulness of the intervention. The experimental patients were found to possess greater information than the 37 patients who signed the form after the usual clinic procedure in virtually every area required of informed consent. The most significant gains were made in patients' understanding of proposed treatment procedures and appropriate treatment alternatives. Women recalled more information relevant to informed consent than did men. Results also indicated a tendency for younger patients to recall more informed consent information than older patients.


Iatrogenic lactic acidosis: association with hypertonic glucose administration in a patient with cancer. A case of lactic acidosis associated with the administration of hypertonic glucose to a patient with a bulky undifferentiated carcinoma is presented. Characteristic alterations in amino acid concentrations were observed during the period of lactic acidosis. Resolution of the metabolic abnormalities were seen with discontinuation of glucose infusion. Short-term glucose infusion in a 90 minute iv glucose tolerance test resulted in an increase in serum lactate and appropriate changes in serine, ornithine, taurine, alanine, and arginine despite normal hormonal responsiveness.


Malignant melanoma in spouses.

Malignant melanoma in spouses. A study of three married couples where both spouses developed malignant melanoma was undertaken at the New York University-Bellevue Medical Center melanoma registry. An upper bound was calculated for the number of spouses expected to develop melanoma, along with the origin of the disease and its relation to nation-wide rates of incidence. The observed number was six times greater than the bound.


Cancers among users of preparations containing vitamin A: a case-control investigation. The frequency of regular use of Vitamin A preparations was compared among 800 newly diagnosed cancer patients and 3433 patients with certain nonmalignant conditions. Overall there was no convincing evidence that regular consumption of such preparations protected against the development of cancer (risk ratio 0.85). However, there was a suggestion of a negative association among men (risk ratio 0.54, p less than 0.01) but not among women (risk ratio 1.11). The negative association among men did not increase with the period that such preparations had been regularly taken and was not greater for squamous cell tumors. The results of this study offer encouragement for further epidemiologic studies of the possible protective role of Vitamin A against cancer.


Marked differences in the carcinogenic activity of optically pure (+)- and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene in newborn mice. Optically pure (+)- and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrenes [(+)- and (-)-BP 7,8-dihydrodiol] were tested for carcinogenicity by giving newborn mice i.p. injections of 20, 40, and 80 nmol of compound on Days 1, 8, and 15 of life. The animals were killed at 17 weeks of age. Control mice had 0.10 pulmonary adenoma per mouse, whereas animals treated with (+)-BP 7,8-dihydrodiol and (-)-BP 7,8-dihydrodiol had 0.16 and 9.28 pulmonary adenomas per mouse, respectively. When a 5-fold higher dose was administered according to the above dosage schedule, (+)-dihydrodiol caused 2.34 pulmonary adenomas per mouse and (-)-BP 7,8-dihydrodiol caused 32.2 pulmonary adenomas per mouse. When 200, 400, and 800 nmol of benzo(a)pyrene or (+)-BP 7,8-dihydrodiol were administered sequentially on Days 1, 8, and 15 of life, 4.13 and 18.5 pulmonary adenomas per mouse, respectively, were observed when the mice were 17 weeks of age. This high dose of (-)-BP 7,8-dihydrodiol killed most of the mice. Administration of (-)-BP 7,8-dihydrodiol caused a high incidence of malignant lymphomas, whereas (+)-BP 7,8-dihydrodiol and benzo(a)pyrene had little or no ability to cause malignant lymphomas.


Effect of Corynebacterium parvum on the proliferative rate of granulocyte-macrophage progenitor cells and the toxicity of chemotherapy. We have studied the interaction of Corynebacterium parvum and a variety of cell cycle-specific and cell cycle-nonspecific chemotherapeutic agents on granulocyte-macrophage progenitor cells [colony-forming units culture (CFU-c)] in C57BL/6 mice. In vitro tritiated thymidine suicide studies showed an increased rate of proliferation of bone marrow CFU-c 24 hr after C. parvum injection. In vivo toxicity of cell cycle-specific agents but not of cell cycle-nonspecific agents for bone marrow CFU-c was increased 24 hr after C. parvum injections. The increased numbers of CFU-c in the spleen, induced by C. parvum, were also sensitive to a cell cycle-specific agent for up to 7 days after C. parvum injection. The findings suggest differences in the kinetics of proliferation of splenic compared to bone marrow CFU-c. The relative time of administration of chemotherapy and immunostimulants such as C. parvum will have to be carefully considered in the design of clinical trials.


Structure-activity study of the inhibition of microtubule assembly in vitro by podophyllotoxin and its congeners. This study investigates the inhibition of microtubule assembly in vitro by podophyllotoxin and its derivatives, which include in part the antitumor compounds 4'-demethylepipodophyllotoxin ethylidene beta-D-glucoside (VP-16-213) and 4'-demethylepipodophyllotoxin thenylidene beta-D-glucoside (VM-26); the cyclic ethers, cyclic sulfides, and cyclic sulfones of podophyllotoxin and deoxypodophyllotoxin; epipodophyllotoxin; picropodophyllotoxin; and several 4'-demethyl compounds. The inhibitory activity of these derivatives is sensitive to the configuration and size of substituents at position 4 in ring C and to steric features of substituents at position 12 in ring D. Decreasing activity correlates with the increasing size of the substituent at position 12, as indexed by their van der Waals radii. These results suggest that rings C and D of these drugs are involved in their interaction with the podophyllotoxin-binding site in tubulin.


Differential regulation of alpha-lactalbumin and casein messenger RNA's in mammary tissue. Rat caseins were characterized with respect to moleculare weight and carbohydrate and amino acid content. Messenger RNA was extracted from rat mammary glands at 5, 10, 15, and 20 days of pregnancy and at 2, 8, and 15 days of lactation and translated in a wheat germ cell-free system. Nascent [3H]casein and alpha-[3H]actalbumin were precipitated separately with specific antibodies and identified by their mobilities on sodium dodecyl sulfate:acrylamide gels and by competition with unlabeled casein and alpha-lactalbumin, respectively. Casein messenger rose continuously from Day 5 of pregnancy to Day 15 of lactation. In contrast, alpha-lactalbumin messenger RNA levels remained low during pregnancy but rose markedly during lactation.


Fifty-five percent complete remission of mammary carcinoma in mice with 5-fluorouracil and chloroquine. Injection of 5-fluorouracil (5-FUra) [12 mg/kg i.p. (0.1 ml) every other day] and chloroquine phosphate (CP) [10 mg/kg i.p. (0.1 ml) daily] after the 19th day postimplant brought about a 55% complete remission of mammary carcinoma (C3HBA) in 2 separate experiments. FUra used alone brought about 40% complete tumor remissions, whereas CP used alone resulted in 30% complete remissions. None of these tumors reappeared before 189 days postimplant in Experiment 1 and 120 days postimplant in Experiment 2. The 5-FUra + CP treatment showed statistically (P less than 0.05) smaller tumor sizes compared to control mice tumor sizes on each of 13 check days after treatment was begun. The CP-treated tumors were statistically smaller than the control tumors on 10 check days, whereas the 5-FUra-treated tumors were smaller than the control tumors on 9 check days. The 5-FUra-treated tumors were statistically smaller than the CP-treated tumors on 2 check days (23 and 33). The 5-FUra + CP-treated tumors were statistically smaller than the CP-treated tumors on 3 check days (36, 43, and 47), and the 5-FUra + CP-treated tumors were statistically smaller than the 5-FUra-treated tumors on the last 4 check days (54, 57, 61, and 64).


Breast cancer at a psychiatric hospital before and after the introduction of neuroleptic agents. No association between breast cancer and treatment with neuroleptic agents agents was detected in a study of 5463 women who died or underwent breast biopsy at the Norristown State Hospital between 1940 and 1974. The method of proportionality was used to evaluate the frequency with which breast cancer occurred at the hospital; cases of breast cancer were related to deaths from other cancers and to deaths from all causes other than breast cancer. Deaths and cancers that occurred within 1 year of hospital admission were excluded from the analysis. To allow for a 10-year transition period and for latency in the development of breast cancer, comparison was made between the 15 years preceding the introduction of neuroleptic agents into medical practice (1940 to 1954) and the second decade after the introduction (1965 to 1974). Although neuroleptic agents were used extensively for treatment of patients at the hospital, there was no statistically or medically significant change in the indicated incidence of breast cancer at the hospital during the neuroleptic period. The study did not rule out the possibility that neuroleptic agents might have some effect on breast cancer after a very long latency period.


Differential response of cultured mouse mammary cells of varying tumorigenicity to cytochalasin B. Cultured BALB/c mouse mammary gland epithelial cells of varying oncogenic potential in vivo have been examined for their ability to multinucleate in the presence of cytochalasin B (CB). Highly tumorigenic cell lines derived from mammary tumors with hormonal, viral, or chemical carcinogen etiologies were extensively multinucleated when cultured in CB-supplemented medium. Normal mammary gland cells from either pregnant or lactating animals were predominantly mono- or binucleate under comparable conditions. At low passage levels after cloning, cell lines derived from a chemical carcinogen-induced mammary tumor were weakly oncogenic and remained largely mono-, or binucleated when cultured in CB-supplemented medium. At higher cell passage levels, both the ability to produce tumors in vivo and the degree of multinucleation in CB-supplemented medium increased dramatically with the clonal cell lines. Thus, the response of cultured mouse mammary gland epithelial cells to CB in vitro may be useful as a marker of the oncogenic potential of such cells.


A preliminary study of the superoxide dismutase content of some human tumors. The cell cytosol superoxide dismutase (SODase) content of 46 human tumors was investigated. The extraction procedure of McCord and Fridovich was used with the epinephrine assay of Misra and Fridovich (J. Biol. Chem., 247; 3170-3175, 1975). The purpose of the study was to determine whether SODase could be reliably assayed from small, biopsy-sized pieces of tumor (0.5 to 1.0 g). In most cases it was possible to examined larger masses of tumor, which served as a control of the methodology. In this preliminary study SODase values, calculated from a standard curve derived from purified bovine blood SODase with a specific activity of 2584 units/mg, ranged from as little as 0.23 to as much as 160.5 units/g of tumor. These findings suggested that the procedures used might be feasable on a routine basis to determine the SODase content of tumors and its possible relationship to the radiation sensitivity of the tumors.


Deoxycytidine kinase and cytosine nucleoside deaminase activities in synchronized cultures of normal rat kidney cells. Previous work has suggested that 1-beta-D-arabinofuranosylcytosine 5'-triphosphate is the active metabolite of 1-beta-D-arabinofuranosylcytosine. The amount of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate formed in tissues has been shown to be influenced by the relative levels of deoxycytidine kinase and cytosine deaminase. In this study we have measured the intracellular levels of deoxycytidine kinase and cytosine deaminase activities in synchronized cultures of normal rat kidney cells. The deoxycytidine kinase activity was found to be cell cycle related with a minor peak of activity in early G1 phase and a major peak of activity in middle and late S phase. The cytosine deaminase activity was also found to be cycle dependent with a peak of activity at G1 phase and another at S phase of the cell cycle. Similar results were obtained when cytosine deaminase activities were measured with cytidine, deoxycytidine, or 1-beta-D-arabinofuranosylcytosine as substrate. Present studies also confirmed earlier studies by other workers that the main effect of 1-beta-D-arabinofuranosylcytosine is in the late S phase of the cell cycle.


Lactate dehydrogenase in estrogen-responsive human breast cancer cells. Lactate dehydrogenase activity (LDH) was measured in the MCF-7 human breast cancer cell line derived at the Michigan Cancer Foundation from a patient with metastatic breast adenocarcinoma. LDH was found in the 46,000 X g supernatant of cell lysates, but not in the culture medium. Only the fifth isozyme (LDH-5) could be demonstrated by cellulose acetate electrophoresis and relative heat inactivation studies. When endogenous steroids were removed from the medium, addition of estrogen to the growth medium for several days elevated LDH 2-fold above controls; LDH was not altered when MCF-7 cells were treated with progesterone, hydrocortisone, prolactin, insulin, or triiodothyronine. A physiological concentration (0.1 nM) of 17beta-estradiol was sufficient to produce a maximal LDH increase. There were no qualitative isozyme changes in response to estrogen. LDH activity may therefore be a useful marker protein for studying hormone action in the MCF-7 human breast cancer cell line.


Glycoprotein synthesis and secretion in human colon cancers and normal colonic mucosa. Glycoprotein synthesis and secretion were measured in short-term organ culture of normal and neoplastic colonic mucosa from 11 patients undergoing colectomy for colon cancer. Mucosal explants were incubated for up to 24 hr with [3H]glucosamine, which was incorporated into both explant and secreted glycoproteins. Structural and functional viability was documented by morphological studies that showed excellent preservation of architectural detail and biochemical studies that documented a steady increase in glycoprotein synthesis during 24-hr incubation. The major difference between normal and neoplastic mucosa was a 35% decrease (p less than 0.02) in the incorporation of [3H]glucosamine into tumor explants, as compared to the amount incorporated into normal explants from the same patient. The rate of secretion of radiolabeled glycoproteins into the medium did not differ significantly. Separation of explants into particulate and cytosol fractions showed that the overall decreases in glycoprotein synthesis in tumor explants was primarily due to a marked reduction in particulate glycoprotein synthesis in the cancer tissue.


Scanning electron microscopic observation of two retinoblastoma cell lines. Two continuous retinoblastoma cell lines were observed by scanning electron microscopy. Both cell lines spontaneously grow as a suspension of round cells in clusters, chains, and unique ring (rosette) formations. Scanning electron microscopy of suspension cells reveals some variation in the number and frequency of surface adornments such as blebs, lamellipodia, and microvilli. Although the cell lines are nonadherent to substratum and therefore assume a spherical form, highly villous cells are not characteristic of the entire cell populations. When WERI-Rb1 and Y79 are seeded onto a polyornithine-treated substrate, attachment and growth as adherent cultures are evident. With selective attachment on a positively charged substrate, we observe alteration of membrane architecture with the extension of cytoplasm and filopidia. In addition, WERI-Rb1 cell-to-substratum adhesion induces morphological changes suggestive of neuronal cell differentiation.


High estrogen and low progestin receptor levels in outgrowths of hypophyseal isografts. Markedly enlarged pituitary isografts in mice contain high concentrations of estrogen receptors and low concentrations, if any, of progestin receptor. This finding is consistent with previous observations that estrogen increases the isograft growth and prolactin secretion while progestin does not. Both types of evidence indicate that in this model system estrogens act indirectly on mammary tumorigenesis by enhancing prolactin secretion in the pituitary isograft and perhaps also the hypophysis in situ, whereas progesterone acts directly on the mammary gland itself.


Effects of retinoic acid and juvenile hormone on the induction of ornithine decarboxylase activity by 12-O-tetradecanoylphorbol-13-acetate. The tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA), a highly active comitogen in phytohemagglutinin-treated bovine lymphocytes, induces an 11-fold increase in ornithine decarboxylase activity over cultures treated with the lectin alone. This synergistic action of TPA could be antagonized by the simultaneous addition of the acyclic sesquiterpene, insect juvenile hormone III. Retinoic acid (vitamin A acid), an inhibitor of the tumor-promoting action of TPA in mice, was also an effective antagonist but required administration to lectin-activated lymphocytes 1 hr prior to TPA. These data suggest that metabolic activation of retinoic acid is required in order to exert its antagonistic action. Comparison of the responses in the lymphocytes and mouse skin suggests that the lymphocytes provide an excellent system for studying the molecular processes through which phorbol esters and retinoids influence the growth and differentiation of both normal and premalignant cells.


A double-blind study on the effect of purified cellulose dietary fiber on 1,2-dimethylhydrazine-induced rat colonic neoplasia. The incidence, distribution, size, and histopathology of grossly visible colonic tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats fed either a chemically defined fiber-free diet or a nutritionally and calorically equivalent diet containing a purified fiber component, microcrystalline cellulose. This double-blind study indicates that cellulose ingestion was associated with reduced numbers of animals involved with colonic neoplasia as well as a reduction in the total numbers of colonic tumors. Furthermore, this protective effect of cellulose appears to be time dependent and associated with a shift in tumor distribution from the proximal colon to a more distal site. Cellulose fiber had no apparent effect on colonic tumor size, histopathology, or the incidence of other tumors known to occur in this experimental animal model. This study strongly supports the hypothesis that fiber is an important protective agent against colonic neoplasia development. While the mechanism for this protective effect remains obscure, it appears to be temporally related to the duration of fiber ingestion as well as to a differential fiber effect on either the luminal content or the mucosa of the proximal and distal colon.


Localized changes in blood-brain barrier permeability following the administration of antineoplastic drugs. The effects of four antineoplastic drugs on the permeability of the blood-brain barrier to Evans blue-albumin and to horseradish peroxidase were studied in cats. Extravasation of tracer in brain tissue was observed only rarely following the injection of methotrexate, cyclophosphamide, or vincristine. However, 5-fluorouracil (15 mg/kg) caused localized Evans blue-albumin exudation in various gray and white matter areas in 8 of 13 cats to which the Evans blue was administered 7 hr after the drug injection. Electron microscopy revealed that 5-fluorouracil stimulated pinocytotic vesicular transport of peroxidase across brain capillary endothelial cells and possibly that it widened endothelial tight junctions. Barrier leakage was not observed when time periods longer than 7 hr elapsed between 5-fluorouracil injection and tracer administration, and extravasation occurred only once after a shorter time interval. These results suggest that changes in blood-brain barrier permeability observed 7 hr after 5-fluorouracil administration are reversible and of fairly short duration. Such changes may be relevant to the development of secondary intracranial tumors following antineoplastic chemotherapy.


Selective potentiation of hyperthermic killing of hypoxic cells by 5-thio-D-glucose. The modification of cell lethality at elevated temperatures by 5-thio-D-glucose, the nearest analog of D-glucose was studied with the use of HeLa cells in the presence or absence of oxygen. When the cells were exposed to temperatures ranging from 40.5-42 degrees for 0.5 to 4 hr in the presence of 5-thio-D-glucose (5 mM), there was a selective potentiation of hyperthermic killing of hypoxic cells. No enhanced killing of oxic cells by 5-thio-D-glucose was seen at these temperatures. These results indicate that glucose metabolism may be involved in influencing the heat sensitivity of hypoxic cells. The low toxicity of 5-thio-D-glucose and its specificity to hypoxic cells suggest that it may be a useful adjuvant to hyperthermic therapy.


Relationships between carcinogenicity and theoretical reactivity indices in polycyclic aromatic hydrocarbons. Theoretical reactivity indices have been used to examine the metabolic reactions presumed, on the basis of recent biochemical evidence, to be responsible for the transformation of polycyclic aromatic hydrocarbon precarcinogens to ultimate carcinogens. Of a large number of indices examined, several show strong correlations with carcinogenic activity in a set of 25 representative compounds. The results support the belief that specific transformations involving dihydrodiol, "bay-region" epoxide, and carbonium ion intermediates are responsible for the carcinogenic activity of these compounds. Additional implications of the results are discussed, including the suggestion that this type of analysis might provide a rapid and simple means for prescreening compounds for potential carcinogens.


An in situ method for estimating cell survival in a solid tumor. The response of the murine Meth-A fibrosarcoma (a methylcholanthrene-induced tumor) to single and fractionated doses of X-irradiation, actinomycin D chemotherapy, and/or concomitant local tumor hyperthermia was assayed with the use of an in situ method for estimating cell kill within a solid tumor. The cell survival assay was based on a standard curve plotting number of inoculated viable cells (10(1) to 10(7)) with and without radiation (10 kilorads)-inactivated homologous tumor cells (heavily irradiated) versus the time required for i.m. tumors to grow to 1.0 cu cm. The time for post-treatment tumors to grow to 1.0 cu cm was cross-referenced to the standard curve, and the number of surviving cells contributing to tumor regrowth was estimated. The resulting surviving fraction curves closely resemble those obtained with in vitro systems. The advantages and limitations of this technique are discussed as a method for evaluating treatment effectiveness.


Induction of tumors in heterotopic bladder by topical application of N-methyl-N-nitrosourea and N-butyl-N-(3-carboxypropyl)nitrosamine. The heterotopic urinary bladder with a communicating reservoir is a potentially useful model for bladder carcinogenesis studies. As a test of whether such bladders will develop transitional cell carcinomas after chronic carcinogenic stimuli, two carcinogens, N-methyl-N-nitrosourea and N-butyl-N-(3-carboxypropyl)nitrosamine, were instilled repeatedly into the reservoir connected with the heterotopic bladder. Transitional cell carcinomas developed in 25 of 33 heterotopic bladders exposed to cumulative doses of 1.5, 3.0, or 6.0 mg of N-methyl-N-nitrosourea for between 20 and 30 weeks, while heterotopic bladders exposed to cumulative doses of 150 or 300 mg of N-butyl-N-(3-carboxypropyl)nitrosamine failed to develop tumors. However, 11 of 27 rats with heterotopic bladders that were exposed to N-butyl-N-(3-carboxypropyl)nitrosamine for over 20 weeks developed tumors in their homotopic or natural bladders. N-Methyl-N-Nitrosourea probably acted directly on the bladder epithelial cells to induce neoplastic change. The reason(s) for the development of tumors in homotopic but not heterotopic bladders when N-butyl-N-(3-carboxypropyl)nitrosamine was administered directly into the heterotopic bladders could not be ascertained from these studies.


Anovulation and increased androgenic activity as breast cancer risk in women with fibrocystic disease of the breast. The urine of 26 otherwise healthy women with fibrocystic disease of the breast was assayed by gas chromatography for testosterone and androstanediol (5alpha-androstane-3alpha, 17beta-diol), the major metabolite of dihydrotestosterone. The mean values for both androgens were significantly higher than in 18 normal women in the same age range. Sixteen of the 26 fibrocystic disease patients also had endometrial hyperplasia. Since the endometrial specimen was obtained in the premenstrual period, the presence of hyperplasia proved that the menstrual cycle in over two-thirds of the fibrocystic disease patients was nonovulatory.


Excretion of spermidine from BHK-21/C13 cells exposed to 6-thioguanosine. The growth of BHK-21/C13 cells in monolayer cultures was inhibited by 6-thioguanosine. Accumulation of putrescine, spermidine, and spermine was inhibited by 6-thioguanosine, and cells incubated in the presence of the drug had a decreased content of polyamines relative to control cells. These effects were more marked for spermidine than for spermine or putrescine. Consequently, the intracellular spermidine:spermine molar ratio was decreased in cells exposed to the drug. Cells, the polyamines of which had been labeled with [3H]putrescine, were incubated in the presence or absence of 6-thioguanosine. More polyamines were lost from cells exposed to the drug than from control cells. The radioactive material excreted was predominantly spermidine, both as its free form and in a conjugated form, even when the cells contained large amounts of labeled spermine. This release of spermidine from BHK-21/C13 cells into the culture medium was a specific response of the cells to alterations in growth potential rather than a consequence of leakage due to cell lysis.


DNA alkylation in mice with genetically different susceptibility to 1,2-dimethylhydrazine-induced colon carcinogenesis. The formation and persistence of methylated purines was determined in mice that received a single s.c. injection of 1,2-[14C]dimethylhydrazine (15 mg/kg) and were allowed to survive for 12 or 60 hr. In mice with a low susceptibility to dimethylhydrazine-induced colon carcinogenesis (C57BL/Ha), concentrations of 7-methylguanine and O6-methylguanine in DNA of colon, ileum, and kidney were 40 to 60% less than in mice with a high incidence of colonic tumors (ICR/Ha). In hepatic DNA the extent of methylation was higher in C57BL/Ha than in ICR/Ha mice. The rate of loss of methylated purines from colon DNA was similar in both strains. In all organs investigated the metabolic incorporation of 14C into normal DNA bases was lower in C57BL/Ha than in ICR/Ha mice. It is concluded that the low carcinogenic response of C57BL/Ha mice is due to the smaller extent of initial alkylation of colon DNA, which probably reflects differences in the enzymic metabolism of the parent carcinogen.


A typical dermatan sulfate isolate from whale intestine. Alkaline extraction of whale intestine, followed by pronase digestion and precipitation of heparin (omega-heparin) with dodecyltrimethylammonium chloride gave a supernatant fraction containing dermatan sulfate. Ethanol at 20% concentration precipitated dermatan sulfate from the supernatant fraction. The crude dermatan sulfate was further fractionated by ion-exchange column chromatography on Dowex-1 (C1- form), eluting stepwise with aqueous sodium chloride. The fractions eluted with 1.5M and 1.75M sodium chloride contained a typical dermatan sulfate. Chemical and enzymic studies of these preparations revealed that the sulfate groups were located solely at O-4 of the 2-acetamido-2-deoxy-D-galactose resides. L-Iduronic acid was assumed to be distributed uniformly in the backbone of the polysaccharide chain, with D-glucuronic acid being located in the linkage region to the protein core. A new method for determining the ratio of D-glucuronic to L-iduronic acid is also described.


Purification of intracellular dextranases and D-glucosidases from pseudomonas UQM 733. The intracellular enzymes of Pseudomonas UQM 733 which act on dextran have been re-investigated mainly by isoelectric focusing. At least three dextranases are present, and one of them (D4) has been purified and shown to be very similar to one of the extracellular endo-dextranases (D1), Three different alpha-D-glucosidases have also been purified.


Structure of some oligosaccharides derived from rat-intestinal glycoproteins. Glycoproteins derived from intestinal mucus were isolated by phenol-water extraction of feces from germ-free rats. The water-soluble glycoproteins were subjected to alkaline-borohydride degradation, and three different oligosaccharide alditols were isolated. The structures of thse were determined by using methylation analysis and n.m.r. spectroscopy as the principal methods. One disaccharide alditol and one trisaccharide alditol were characterised as beta-D-GlcNAcp-(1 leads to 3)-D-GalNAcol and alpha-L-Fucp-(1 leads to 2)-beta-D-Galp-(1 leads to 3)-D-GalNAcol. The third oligosaccharide alditol was a blood-group A-active tetrasaccharide alditol for which the structure alpha-D-GalNAcp-(1 leads to 3)-[alpha-L-Fucp-(1 leads to 2)]-beta-D-Galp-(1 leads to 3)-D-GalNAcol is proposed.


Structural studies of a specific polysaccharide isolated from non-agglutinable Vibrio. The purified, specific polysaccharide from Vibrio cholera type NAG, NV 384, O-antigen, 2A, 2B human, contains glucose (5.14%), galactose (4.21%), mannose (64.8%), xylose (3.16%), arabinose (1.98%), fucose (1.50%), mannuronic acid (14.3%), phosphate (0.32%), 2-amino-2-deoxy-D-glucose (2.9%), and 2-amino-2-deoxy-D-galactose (1.0%). Various reactions have shown that the material comprises a phosphoric diester-linked polysaccharide containing mainly ( 1 leads to 2)-linked mannopyranose residues that are highly branched with other sugar residues.


Cardiovascular changes in awake dogs caused by suddenly induced aortic hypertension. Cardiovascular adaptation to the sudden inflation of a balloon in the descending aorta was investigated in intact awake, standing dogs. The balloon inflation raised pressure in the arterial bed proximal from the balloon. Initially, it lowered heart rate and cardiac output. After 4 sec, heart rate and cardiac output began increasing again and within the next 14 sec, these functions returned almost to the control values. The restoration of cardiac output was associated with a further rise in aortic pressure. These findings are consistent with the hypothesis that the prime circulatory adaptation to a hindrance to arterial flow is restoration of blood flow even though this requires a further elevation of arterial pressure. The demands of the tissues for an adequate supply of blood appear to override the inhibitory baroreceptor reflexes. The circulatory changes observed under conditions of attenuated parasympathetic inhibition and under conditions of attenuated beta-adrenergic stimulation were consistent with this interpretation. The findings suggest that arterial hyertension may involve a comparable adaptation of cardiac output in patients whose blood flow is hindered by pathologically narrowed arterioles.


An analysis of cholinergic involvement in postvagal tachycardia. The role of acetylcholine (ACh) in the sinus tachycardia which follows vagal stimulation ('postvagal tachycardia') was investigated in anesthetized dogs. The stimulation of either vagus was followed by postvagal tachycardia. The bradycardia induced by local application of ACh to the sinus node was followed by sinus tachycardia while local application of methacholine (a predominantly muscarinic agonist) induced only bradycardia. Atropine potentiated the postvagal tachycardia in low doses and blocked it in high doses. The conclusion drawn is that postvagal tachycardia is caused by the release of ACh by either vagus acting on a nicotinic receptor.


Sipple's syndrome with a malignant pheochromocytoma presenting as a pericardial effusion. Sipple's syndrome is a multiple endocrinopathy usually involving the adrenal medulla and the thyroid. In the present case, a malignant pheochromocytoma metastasized to the pericardium and both lungs. The patient was known to have had a calcified right suprarenal mass for 8 years. He was admitted to the emergency room with symptomatology consistent with pericardial tamponade, but despite intensive management, he expired.


Different prognostic value of exercise electrocardiogram in men and women. In 1,455 subjects (947 men and 508 women) who underwent a bicycle ergometer stress test for evaluation of atypical chest pain, the incidence of coronary events (definite myocardial infarction or sudden death) was assessed by the life table method. The follow-up period ranged from 3 to 7 years (mean 5.2 years). In men with positive exercise test (ischemic ST depression greater than or equal to 1 mm), the 5-year incidence of coronary events was 18.3%, compared with 1.9% in negative responders. In women with positive response, the 5-year incidence of coronary events was 4.6%; in negative responders, it was 0.3%. The poor predictive value of ischemic ST responses to exercise in women is emphasized.


Effect of hydrostatic pressure on isolated cardiac nuclei: Stimulation of RNA polymerase II activity. RNA polymerase activity was measured in isolated cardiac nuclei subjected to hydrostatic pressure. After 20 min of pressure, Mn2+ stimulated RNA polymerase II activity was increased. The response to pressure was inhibited by low concentrations of alpha-amanitin (1.1 microgram.cm-3) an inhibitor of polymerase II activity. The data show that pressure applied to isolated nuclei stimulates RNA polymerase II activity, forming mRNA, and suggests that direct application of pressure to cardiac nuclei may be the stimulus which triggers the augmented protein synthesis seen in pressure overload.


Haemodynamic effects of static and dynamic exercise in males with arterial hypertension of varying severity. Sustained handgrip at 30% of the maximal strength and submaximal supine bicycle exercise elicited mean blood pressure increases of similar magnitude in healthy males and in men with essential hypertension WHO Stage 1 and 2, but with different contributions of systolic and diastolic blood pressure changes. While systolic blood pressure exceeded 22.7 kPa (170 mmHg) during static exercise in every hypertensive man, this did not occur in any of the control subjects. During dynamic exercise, the arterial blood pressure increase per litre increase in cardiac output was significantly less than during static exercise, indicating different patterns of circulatory adaptation to these two forms of stress. Combination of dynamic and static exercise tests might be of value for identifying subjects with a hypertensive pattern of circulatory regulation.


Relation between pressure difference across the aortic valve and left ventricular outflow. Equations are presented to relate left ventricular-aortic pressure difference and flow. The relative importance of fluid inertia and friction are evaluated and the errors introduced by the neglect of compliance are estimated. The equations are used to calculate pressure differences for both normal conditions and simulated aortic stenosis and to explain the timing of the reversal of the pressure difference.


Effect of digitalis on human ventricular refactoriness. In order to evaluate the effect of digitalis on the effective refractory period of the human ventricle, 14 patients were studied with atrial or ventricular pacing and with the introduction of ventricular extra-stimuli. The ventricular effective refractory period (VERP) was recorded before and after 1.0 to 1.25 mg ouabain given intravenously and the results compared with similar changes in the Q-T interval. During atrial pacing (eight patients) at rates of 70 to 110 beats per minute, ouabain reduced the mean ventricular effective refractory period from 290 +/- 13 ms to 260 +/- 16 ms (P less than 0.01) and the mean Q-T interval was reduced from 372 +/- 18 ms to 359 +/- 19 ms (P less than 0.01); the mean VERP/Q-T ratio was 0.79 +/- 0.04 before ouabain and 0.73 +/- 0.04 after ouabain (P less than 0.01). Utilising ventricular drive pacing (six patients) the mean ventricular effective refractory period was reduced from 245 +/- 16 ms to 226 +/- 13 ms (P less than 0.01) and the mean Q-T interval reduced from 382 +/- 18 ms to 360 +/- 29 ms (P less than 0.01). There was no significant change in the mean VERP/Q-T ratio (0.63 +/- 0.04 before vs 0.63 +/- 0.04 after ouabain). The results demonstrate that clinically effective doses of ouabain produce a significant reduction of the effective refractory period of the human ventricle. This change is accompanied by a reduction in the VERP/Q-T ratio during atrial pacing.


Comparative haemodynamic and metabolic effects of vasodilator and inotropic agents in experimental myocardial infarction. Following coronary embolisation and onset of left ventricular failure 27 awake dogs were randomly assigned to infusion of saline (controls), nitroprusside, or dobutamine (a new inotropic agent). Nitroprusside and dobutamine both increased cardiac output and lowered left ventricular filling pressure while raising coronary sinus flow. Dobutamine, however, increased myocardial oxygen consumption whereas nitroprusside reduced it. Therefore vasidilators may be more beneficial than inotropic agents in acute myocardial infarction.


Functional role of collateral flow in the ischaemic dog heart. Studies were carried out in four different canine preparations to determine the effect of collateral flow on early changes induced by acute segmental ischaemia. The results of these experiments indicated that collateral flow provided a limited and variable amount of protection. When collateral flow was eliminated, myocardial cell injury was more severe and less variable.


An analogue device for the measurement of cardiovascular variables. An analogue device is described which is designed to analyse repetitive signals. It measures peak amplitudes, time to peak values, areas, and values at a preset time. The results can be displayed or recorded on a beat-to-beat basis, or an average can be taken over up to 31 consecutive beats.


Quantitative analysis of squamous epithelium of normal palatal mucosa in guinea pigs. The epithelium of intact guinea pig palate was subjected to stereologic analysis in a study of structural alterations in the keratinizing epithelium in response to wounding. Point counting procedures were employed to analyse electron micrographs sampled from three epithelial strata in biopsies collected from five animals. The differentiation pattern of the guinea pig palate epithelium displayed the following structural density gradients from basal to granular layers: descending gradients of metabolically active organelles, ascending gradient of bundled filaments coupled with the appearance of membrane coating granules and keratohyalin granules, and a plateau-like gradient of cytoplasmic ground substance. This pattern of epithelial differentiation is basically identical to that of human hard palate epithelium and epidermis. Regional and species variations in structure of keratinizing epithelia are suggested based on interepithelial differences in morphometric parameters.


Structural re-evaluation of the neurosecretory system in the crayfish eyestalk. The topography of the neurosecretory system in the decapod eyestalk has not been precisely delineated with light microscopy. Cobalt iontophoresis and electron microscopy have proved useful in clarifying the microstructure of this system. The sinus gland (sg) of the crayfish eyestalk consists of aggregated axon terminals which end at or near the blood space. Iontophoresing cobalt back through the cut base of the sinus glands reveals proximal cell bodies in the eyestalk only in the X organ (Xo) region. Electron microscopy demonstrates that axons from about 115 neurosecretory cell bodies in the Xo form the Xo-sg tract. Intermingled with these Xo somata are smaller non-neurosecretory cell bodies which do not send axons into the sinus gland. One of these exhibits catecholamine fluorescence. Backfilling also reveals a second group of fibres which run from the brain along the optic tract and into the sinus gland. These brain-sg fibres are smaller in diameter than Xo-sg axons and lack neurosecretory vesicles. From these fibres collaterals extend into the eyestalk neuropil, especially in the proximity of the visual elements. The possible function of these non-neurosecretory processes within the sinus gland is discussed.


Effect of stretch and contraction on caveolae of smooth muscle cells. The number of caveolae present at the surface of smooth muscle cells of guinea-pig taenia coli and visualized by freeze-fracture is about 35 per micron2. (By comparison, endothelial cells of intramuscular capillaries have about 73 caveolae per micron2). The packing density of smooth muscle caveolae is not significantly different in muscle strips isotonically contracted with carbachol or stretched and relaxed in a calcium-free solution, under a range of loads varying from 1 to 15 g. Also the diameter of the fractured necks of the caveolae appears unchanged in all the experimental conditions tested. The plasma membrane of smooth muscle cells often shows a ring of intramembranous particles rimming the opening of a caveola; on the other hand, particles are rare in the membrane of the caveolae themselves. The close relation between caveolae and sarcoplasmic reticulum is readily visualized in freeze-fracture preparations. Characteristic changes of the cell surface shape accompany the contraction and relaxation of the muscle. On rare occasions small aggregates of intramembranous particles are found and it is possible that they represent punctate gap junctions. However, the characteristic clusters of particles found in the circular musculature of the caecum and ileum are not seen in taenia coli.


Automatic morphometric analysis of retrograde changes in the nucleus n. facialis at different ontogenetic stages in the rat. The grey level index (= GLI) and the fresh voluem were determined with the image analyser Micro-Videomat for the nucl. n. facialis after axotomy of the left n. facialis. The experiments were performed on 10 rats in different stages of ontogenesis. The GLI is a quantitative parameter which could be quickly obtained and which demonstrated quantitative changes during retrograde reaction in the respective centres. A decrease in the fresh volumes of the affected nucl. n. facialis could also be demonstrated. The meaning of GLI is discussed.


Fine structure and composition of the submucous nerve plexus of the guinea-pig trachea. The ultrastructure of the nerves forming the submucous plexus of cervical and thoracic parts of the trachea was studied in the guinea-pig. Specimens were obtained from 6 animals perfused with warm fixative and from 6 animals in which pieces of trachea were incubated in buffer containing 5-hydroxydopamine before immersed in cold fixative. Of the two types of axonal terminal identified in the nerves, one contained mainly large dense-cored vesicles, and the second contained numerous small vesicles. In specimens incubated in 5-hydroxydopamine, the small vesicles of the latter terminals exhibited the electron-dense cores which are characteristic of adrenergic axonal terminals. Counts made on perfused specimens showed that, in both the thoracic and cervical parts of the trachea, the density of adrenergic terminals was higher than that of terminals containing mainly large dense-cored vesicles. Overall terminal density was, however, higher in the thoracic than in the cervical part of the trachea, and estimates of nerve size showed that this was associated with the presence in the thoracic plexus of a substantially greater proportion of nerves with less than 6 axons. The possible function of the nerves in the control of the calibre of the submucous blood vessels was discussed.


The respiratory epithelium in the lungs of the slow-worm, Anguis fragilis. The epithelium covering the respiratory portion in the lung of the slow-worm (Anguis fragilis) has been studied by electron microscopy. The epithelium is composed of two different types of pneumonocytes. The type I pneumonocytes are roughly squamous and their cytoplasmic sheets spread over relatively large areas of the septal walls. These cytoplasmic sheets are attenuated in regions where they overlie septal capillaries; they usually have extensive areas of contact with adjacent cells. The type II pneumonocytes are also squamous but are more compact and possess more organelles. Their osmiophilic inclusion bodies are especially conspicuous. Most of their microvilli are concentrated on the surfaces of cytoplasmic "hillocks". Deposits of membranous material are present in the air sacs. The morphological evidence suggests that the type II cells of Anguis secrete surface-active material.


Occurrence and regional distribution of striated muscle fibers in the rat pineal gland. In a total of 96 rat pineals studied 31 were found to contain striated muscle fibers or their precursors. The muscle fibers were most frequently present in the stalk region and more frequently found in the left than in the right hemisphere. Size measurements revealed that the lengths of pineal muscle cell nuclei differ only slightly from those of the sphincter muscle of the iris. However, the yellowish appearance of pineal muscle cell nuclei under darkfield investigation, a phenomenon observed in all muscular tissues of mesenchymal origin and connective tissue cells, may support the hypothesis that pineal musculature is of mesenchymal rather than ectodermal origin.


Effect of cyproterone acetate, d-norgestrel and progesterone on cells of the pars distalis of the adenohypophysis in the beagle bitch. The effects of short-term (8 weeks) treatment with different doses of cyproterone acetate (CPA), d-norgestrel (d-N) and progesterone on cells of the pars distalis, as revealed by the immunoperoxidase technique, were studied in cycle-synchronized beagle bitches (first anoestrus). Pituitary glands from non-treated primiparous beagle bitches at the 6th and 9th week of pregnancy were also included. For immunochemical staining specific antisera to the following hormones were used: canine GH, canine PRI, porcine ACTH, bovine TSHbeta, bovine LHbeta and human FSHbeta. Morphological features of high secretory activity in GH cells were evident even after the human oral contraceptive does of CPA and d-N, and after a dose as low as 0.1 mg/kg/day subcutaneously (s.c.) of progesterone. In contrast, PRL cells did not show any significant treatment-related effects except in those animals which received the highest dose of d-N (0.5 mg/kg/day per os). In this group, as well as in all pregnant bitches, hyperplasia and hypertrophy of PRL cells were found. In the animals treated with the highest doses of CPA (4.0 mg/kg/day per os) and progesterone (42.5 mg/kg/day s.c.) as well as in pregnant bitches, ACTH/MSH and TSH cells showed marked atrophy and regressive changes. Similar morphological signs of depressed secretory activity were also observed in the cells shown to contain FSHbeta and/or LHbeta as a result of treatment with the highest dose of progesterone and at the 9th week of pregnancy. These structural responses indicate that quantitiative and/or qualitative differences may exist between progesterone, the synthetic progesterone derivative CPA and the nortestosterone type progestagen d-N with regard to their effect on pituitary hormone secretion in the beagle bitch.


The structure of the nervous system of the pluteus larva of Strongylocentrotus purpuratus. Tissues that have the ultrastructural characteristics of nervous tissues are associated with ciliary and muscular elements of the pluteus larva of Strongylocentrotus purpuratus. The nerve cells are found along the margins of the ciliary bands, which are composed predominantly of spindle-shaped ciliated cells. The nerve cells contribute axonal processes to a tract of axons, which runs at the base of the ciliary band throughout its length. Axonal tracts, in the esophagus, lie beneath the circumesophageal muscles. Branched microvilli, which have been interpreted as sensory receptors, are located on the oral side of the main ciliary band and connect with the nerve cells in the ciliary band. The nervous structures described here, and other tissues of the pluteus that have been previously described as nervous, are compared on the basis of their association with receptor and effector organs, and their ultrastructural characteristics.


Ultrastructural observations on the hypothalamo-posthypophysical complex of the Brattleboro rat. The hypothalamo-posthypophysial complex of the homozygous Brattleboro rat is characterized by a hyperactivity of its neurons. The neurosecretory fibers, especially in the neurohypophysis, show numerous signs of autophagy and tubular proliferation of the axoplasmic reticulum. These structural alterations, as well as the nematosomes of nucleolus-like bodies encountered in the perikarya, may be related to the chronic hyperactivity of the neurons. They can be reduced by administration of exogenous vasopressin. The numerous liposomes in the pituicytes are paralleled in the neuronal perikarya by a great number of lysosomes. Small dense core vesicles observed in the neurosecretory endings and perikarya may indicate a secretory product distinct from oxytocin and vasopressin. In the homozygous Brattleboro rat, endings of the aminergic type are more numerous than in the normal rat. With respect to the role they may play in the secretory processes, their increase might be secondary to the vasopressin deficiency.


Lamellated outer dendritic segments of a sensory cell within a poreless thermo- and hygroreceptive sensillum of the insect Carausius morosus. A sensillum in a narrow pit with a braod cuticular collar, located in a sensillum field on the 12th segment of the antennae of Carausius morosus, was investigated electrophysiologically. After marking, it was also examined with the transmission and the scanning electron microscopes. The number of sensory cells within the sensillum varies between three and four. One cell, present in half of the sensilla studied, exhibits a simple cilium of the 9 x 2 + 0 type as outer dendritic segment. The outer segment of a second unit is noteworthy in that it divides near its ciliary base into two branches. These flatten to form lamellae, then fold and wrap around each other. The remaining two sensory cells bear unbranched or bifurcate outer segments which contain densely packed microtubules. Only these outer segments extend into the cuticular peg; the others end beneath its base. The cuticular peg is devoid of pore systems. Electrophysiological recording yielded evidence that a cold, a dry and a moist air receptor are present. The fourth unit did not respond clearly to stimulation.


Fine structure of degenerating abdominal motor neurons after eclosion in the sphingid moth, Manduca sexta. Ultrastructural aspects of the natural degeneration of a group of six motor neurons in the fourth abdominal ganglion of Manduca sexta are described. These motor neurons innervate intersegmental muscles that degenerate and disappear immediately after adult eclosion. The first detectable changes in the cell bodies appear 12h after eclosion and include disruption of the endoplasmic reticulum and an increase in the size and number of lamellar bodies. At 32h the nuclear membranes rupture, and the membranous and granular cytoorganelles segregate in different parts of the cell. At that stage the surrounding glial cells participate in the digestion of material from the degenerating neurons. From 72h onward the remaining neuronal structures become disrupted, and are finally transformed into a single, large lamellar body (residual body) within the glial profile. The degeneration pattern differs significantly from that of embryonic vertebrate neurons.


Ultrastructural and morphometric study of the lung of the European salamander, Salamandra salamandra L. Ultrastructural and morphometric investigations were performed on the lung of the European salamander, Salamandra salamandra L. Folds of first and second order are covered with a ciliated epithelium containing goblet cells. The respiratory surface of the lung is lined by a single type of cell which, in amphibians, combines features of type I and type II alveolar cells of the mammalian lung. In the salamander the respiratory and ciliated epithelial cells as well as goblet cells possess electron dense and lucent vesicles in their cytoplasm as well as lamellar bodies. A small amount of surfactant, composed most probably of phospholipids and mucopolysaccharides, was observed covering the entire inner surface of the lung. Morphometric methods were used to determine the dimensions of the perinuclear region of pneumocytes, the thickness of the air-blood barrier and lung wall, and also the diameter of capillaries. The thickness of the respiratory air-blood barrier was found to be considerably higher than that of the corresponding barrier in mammals.


Crystalloid structures within giant mitochondria of the prothoracic glands of Spodoptera littoralis (Bois) (Lepidoptera). The fine structure of the prothoracic glands of Spodoptera littoralis was investigated during the first half of the last larval instar. The secretory cells have two types of mitochondria, micromitochondria and macromitochondria. The micromitochondria have rounded to elongated profiles and sometimes branch. They contain lamellar, tubular and also tubulo-vesicular cristae. The macromitochondria appear generally rounded or oval and possess tubular cristae. Many regular parallel membranes appear within macromitochondria. Favorable sections show tubular structures packed in honeycomb fashion. The mitochondrial cristae are in connection with the tubular structures. Honeycomb and parallel membranes increase in number as the size of the macromitochondria increases.


The ontogenesis of calcium-binding protein in fetal rat kidney. The presence of calcium-binding protein (CaBP) in the nucleus and cytoplasm of epithelial cells of renal tubules varies with the physiologic state. As part of a study to determine whether or not intranuclear CaBP precedes intracytoplasmic CaBP in the same cell, we used peroxidase-labeled antibody against human renal CaBP to localize CaBP in fetal rat kidney tubules. This paper reports examination of kidneys from rats on each day of gestation from the 10th to term (21 days) and on each of the first seven postnatal days. CaBP was first detected in fetal rat kidneys on the 19th gestational day. The histochemical staining reaction that revealed the CaBP was less intense than that produced in kidneys from adult animals, but its distribution was like that in adults, with some cells having no CaBP, others having it in the cytoplasm only, in the nucleus only, or in both. By the seventh postnatal day the staining reaction was similar to the adult patterns in all respects.


Stimulation of microsomal dimethylnitrosamine-N-demethylase by pretreatment of mice with acetone. To further investigate the relationship between in vivo microsomal enzyme modifiers and in vitro dimethylnitrosamine (DMN) metabolism, male C57BL/6J mice were pretreated with acetone or Aroclor 1254, two compounds known to influence DMN-N-demethylase activity. Pretreatment with acetone enhanced the in vitro microsomal activity of DMN-N-demethylase, as measured by formaldehyde production from DMN. Accompanying this acetone-enhanced demethylase activity was an increase in the covalent binding of [14C]DMN to RNA, protein and DNA. Four distinct Km values dependent on the substrate concentration were observed for the N-demethylase present in control microsomes. Only one Km value was observed for the demethylase in microsomes from acetone-treated animals, but it was significantly lower than the lowest Km observed in the control microsomes. At DMN concentrations of 1 and 10 mM, acetone significantly increased N-demethylation of DMN as compared to control, but not at 100 mM DMN. Aroclor 1254 pretreatment repressed DMN-N-demethylase at 1 mM DMN but enhanced it at 100 mM. These results suggest that there may be multiple forms of DMN-N-demethylase which are dependent on DMN concentration and respond differently to modifiers of the microsomal drug-metabolizing enzymes.


Influence of cystein deficiency on the inhibition of hepatic microsomal detoxication by methyl mercury in two rat strains. Two rat strains, Wistar, strain R and Sprague--Dawley, were subjected to cystein deficiency and methyl mercury pretreatment, both separately and in combination, after which the hepatic microsomal N- and C-oxygenation of N,N-dimethylaniline (DMA) was studied. Cystein deficiency caused a reduction in C-oxygenation in strain R microsomes, and this reduction was nearly doubled by methyl mercury pretreatment of the depleted rats. Methyl mercury pretreatment per se of strain R rats on the standard diet gave no effect. By contrast microsomes from cystein deficient SpD rats showed no statistically significant decrease in C-oxygenation, and cystein deficiency did not further enhance the inhibitory effect obtained with methyl mercury pretreatment alone. N-oxygenation was not significantly affected by any treatment of the two strains.


Reaction products of the carcinogen N-hydroxy-4-acetylamino-4'-fluorobiphenyl with DNA in liver and kidney of the rat. The binding of AABP4'F and ABP4'F residues to rat liver and kidney DNA in vivo was studied at different periods of time after administration of N-[G-3H]hydroxy-AABP4'F at dose levels of 5 and 25 mg/kg body weight. DNA preparations from both organs were hydrolyzed enzymatically at pH 8--9 with mixtures of DNAase, snake venom phosphodiesterase and alkaline phosphatase from Escherichia coli. The enzymatic digests were analysed by Sephadex LH-20 chromatography using synthetic N-([G-14C] deoxyguanosin-8-yl)-AABP4'F as marker. Elution with 30% ethanol gave three major peaks of tritium activity. The first peak consisted largely of N-(deoxyguanosin-8-yl)-ABP4'F decomposition products, which were not further characterized. The second product has similar chromatographical and chemical properties as 3-(deoxyguanosin-N2-yl)-AAF; and was also persistent in liver as well as in kidneys. The third peak of tritium activity co-chromatographed with the marker compound N-([G-14C] deoxyguanosin-8-yl)-AABP4'F. Kinetic studies revealed that the latter product was removed rapidly from liver and kidney DNA at equal rates (t1/2 = 2 days). Approximately 80% of the total radioactivity bound to DNA consisted of deacetylated material, which was removed at a much slower rate (t1/2 = 10 days) in both organs. An initial rapid removal of all products in kidney during the first 7 days (t1/2 = 3.3 days) at dose levels of 25 mg/kg is probably due to toxic effects on the kidneys, because this phenomenon was not observed at dose levels of 5 mg/kg. The synthetic ester N-OSO3K-AABP4'F was at least twice as reactive towards L-methionine and guanosine as compared to the corresponding AABP derivative, but had 40% of the reactivity of N-acetoxy-AAF under similar conditions. The new compounds 3-methylmercapto-4-acetylamino-4'-fluorobiphenyl and N-(deoxyguanosin-8-yl)-4-acetylamino-4'-fluorobiphenyl have been characterized by means of their NMR and mass spectra. Attempts to devise an unambiguous synthesis for 3-(deoxyguanosin-N2-yl)arylamides have been unsuccessful.


Maleate induced change in the kidney binding of mercury in rats pretreated with cadmium. The kidney uptake of Hg2+ was increased by Cd2+-pretreatment when Hg2+ was given intraperitoneally but not subcutaneously. Subsequent s.c. administration of maleate increased Hg2+ release from the kidneys only if Hg2+ was given subcutaneously. Neither the effect of Cd2+, nor that of maleate, on the distribution of Hg2+ among the renal soluble protein fractions was affected by the route of Hg2+ administration. The protective effect of Cd2+-pretreatment against the nephrotoxic effect of Hg2+ was also independent of the route of Hg2+ administration. Maleate given in nephrotoxic doses removed Hg2+ and copper, but not Cd2+ from the renal metallothionein fraction. Mercury in the urine, however, was not complexed by proteins with the molecular weight of thionein, but was bound to high molecular weight proteins and diffusible molecules. These findings are discussed in relation to the role of metallothionein in the interaction between Cd2+ and Hg2+.


Distribution of a platinum anti-tumour drug in HeLa cells by analytical electron microscopy. The distribution of Pt in HeLa cell sections after cell treatment with cis-Pt(NH3)2Cl2 dissolved in dimethylsulphoxide was probed by analytical electron microscopy. Primary targets were the nucleolus and the inner side of the nuclear double membrane. Even after solvolysis in dimethylsulphoxide the drug reached similar sites. It is suggested that cell death may be due to Pt inhibition at the initiation sites of DNA synthesis.


Dose-response studies of penicillamine and related compounds in reducing skin--tensile strength of rats. Penicillamine (I) and certain related compounds are known to reduce the skin tensile strength (sts) of rat dorsal skin when they are given in the diet. This effect seems significant to studies of the biochemistry of collagen and of diseases of collagen, perhaps including the arthritides. The reduction of sts appears to be caused by diminution of collagen crosslinking. The effects of several such compounds were studied after intraperitoneal (ip) injection, in order to determine structure-activity relationships divorced from possible anorexic or gastrointestinal complications seen after oral dosing, and to examine the relation of ip dose to response. A cyclopentyl analog (II) of I was at least as active as I, showing that structural variants of I can be active when given ip. A dimethylthiazolidine (V) and a zinc chelate (III, rather toxic) of I were nearly as active as I, showing that probable in vivo precursors of I can be obtained that will be active when given ip. The disulfide of I and a zinc chelate of cysteine were inactive. Maximum response for several compounds seemed to occur at intermediate dose levels, with larger or smaller doses affording less sts reduction.


Effects of long-term turpentine inhalation on rat brain protein metabolism. Chronic exposure of adult male rats to commercial turpentine resulted in an accumulation of the solvent in perinephric fat and brain. The body solvent content remained virtually stable during 8 weeks. Brain RNA content was below the control range initially and it increased to the control level at the 4th week of exposure. Serum non-specific cholinesterase activity was somewhat below the control range at the first and second week of exposure and it returned to the control level thereafter. The present data are in agreement with the small effects of turpentine exposure on human central nervous system in clinical follow-up studies.


The preparation of dihydrodiols from 7-methylbenz[a]-anthracene. The products formed when the carcinogenic polycyclic hydrocarbon 7-methylbenz[a] anthracene is oxidized with an ascorbic acid-ferrous sulphate mixture have been investigated. All 5 possible dihydrodiols were formed and the isolation of the 3 non-K-region dihydrodiols, trans-1,2-dihydro-1,2-dihydroxy-7-methylbenz[a]anthracene, trans-3,4-dihydro-3,4-dihydroxy-7-methylbenz[a] anthracene and trans-8,9-dihydro-8,9-dihydroxy-7-methylbenz[a] anthracene is described. The purification of the dihydrodiols was carried out by thin-layer (TLC) followed by preparative high pressure liquid chromatography (HPLC). The ultra-violet, spectral and nuclear magnetic resonance (NMR) characteristics of the dihydrodiols are reported and the data used to assign the proposed structures. An explanation for the unusual preferred conformation which the 8,9-dihydrodiol adopts is advanced.


The metabolism of selenite by intact rat erythrocytes in vitro. 75Se-labeled selenite was used to study its metabolism by intact rat erythrocytes in vitro. Utilizing both N-ethylmaleimide and excess selenite to lower erythrocyte GSH concentrations it was shown that the uptake and subsequent metabolism of selenite was dependent upon GSH. The secondary release of Se by rat erythrocytes had no relation to the erythrocyte transport of GSSG. While fluoride depressed and chromate increased GSSG transport, chromate, a glutathione reductase inhibitor, decreased Se release. This was consistent with the concept that the release was secondary to a reaction catalyzed by gluthathione reductase. The similarity of the I50 values for chromates' irreversible inhibition of glutathione reductase and for the inhibition of Se release further suggested a relationship between these two events. These results supported the hypothesis that H2Se or a similar product of GSSeSG reduction by glutathione reductase was the final product of selenite metabolism by rat erythrocytes.


[Distal termino-lateral spleno-renal anastomosis, using the Warren technic]. The authors describe 23 cases of distal splenorenal derivation after Warren. Of these patients, 17 received a complete followup clinical hematological and angiographic examination at an average remove of 10 months after surgery. The authors discuss their results and submit that the Warren operation, while really selcetive in most cases when performed, in the long run tends to shung rather too much blood away from the liver; in other words, the effectiveness of the shunt tends to exceed the intended drainage,which should be restricted to the gastro-esophageal vascular bed.


[Role of post-embolectomy anticoagulant therapy in the prevention of recurrences]. The authors review two homogenous groups of patients subjected to surgical embolectomy, one group receiving standard anticoagulant therapy before and after surgery, and the other not receiving that treatment regularly or at all. The results obtained in the two groups indicate that anticoagulant therapy plays a role of no mean order in the prevention of postoperative relapses.


[Anastomoses of the lower 3d of the esophagus]. In view of the larger number of operations on the bottom third of the oesophagus recently necessary in the destructive surgical therapy for tumours, the Authors re-examine 50 cases of oesophago-gastric and oesophago-jejunal anastomoses and stress the importance of accurate anastomoses, preferably single-layer in order to avoid early and delayed complications.


[Agenesis of the gallbladder. Presentation of a case]. The authors describe one case of agenesis of the gallbladder associated with papillary stenosis, dyskinesia of the extrahepatic bile ducts, and chronic appendicitis. They devote particular attention to the composition of hepatic bile and choledochal bile, which was investigated in detail after surgical exploration of the extrahepatic bile passages, transduodenal papillosphincterotomy, and appendectomy. They conclude that this rare congenital failure of organ development, in the long run, even a slight alteration of bile composition in the hepatic and/or choledochal segment of the biliary tract (the latter somewhat serving the purpose of the missing gallbladder) may invite calculosis of the common bile duct.


[Neurinoma of the tongue].

[Neurinoma of the tongue]. The authors describe one case of neurinoma of the tongue, recently come to their observation, and offer a clinical and anatomopathological presentation of this heteroplasia. In the light of a careful search of existing literature they estimate the incidence of this tumor both versus neurinoma located elsewhere in the body versus pathological processes located in the tongue. In particular, they call attention to problems of differential diagnosis posed by neurinoma in clinical terms and in the pathologist's laboratory, in relation to other tumors and infectious processes observed in the tongue.


[Some practical diagnostic notes on severe jaundice]. The authors discuss duodenoscopy conduced with the help of a topical anesthetic plus systemic antispasmodic premedication for the differential diagnosis of severe jaundice, with or without catheterization of the papilla. From their first-hand experience with this method, the authors conclude that the procedure is remarkably useful and free of complications.


[Splenectomy: indications and results].

[Splenectomy: indications and results]. The authors review their splenectomy records for the last ten years and discuss complications and mortality in relation to the indications for such surgery in each case. They conclude that both immediate and delayed postoperative mortality reflects mainly the underlying disease rather than surgical trauma; in their clinical material, complications were never severe and at any rate readily brought under control.


[Use of blood and blood derivatives in surgical patients]. In view of the considerable therapeutic significance of blood transfusion in connection with major surgery and of the various problems involved, the author offers a discussion of the best ways to use whole blood and blood derivatives in the surgical patient. First he gives a synthetic outline of the pathophysiology of blood losses; then he sketches a set of guidelines to appropriate remedial treatment; and last, he discusses the risks and drawbacks associated with blood transfusion.


[A case of renal clear-cell carcinoma simulating a renal cyst. Diagnostic and therapeutic considerations]. The authors describe one case of renal cyst with radiological evidence of psammoma-like calcifications. Explored surgically, and even though the liquid content was clear, this cyst revealed the presence of a light-cell carcinoma at the bottom of the cavity. One the strength of this finding, the authors recommend exploratory lumbotomy and opening of the cyst wall in such cases.


Electrotonic interaction during canine ventricular repolarization. Canine ventricular refractory periods were measured during test site drive, during drive of single ectopic sites, during fusion drive from two ectopic sites, and during fusion drive from an ectopic site and the test site. Refractory period duration was dependent on the driving modes employed. Refractory periods were 2.63 +/- 0.73%, 3.42 +/- 0.87%, 3.54 +/- 100%, and 4.68 +/- 1.36% (mean +/- SD) shorter during drive of single ectopic sites 2, 4, 6, and 40-60 mm, respectively, from the test site than during test site drive. During fusion drive from two ectopic sites, refractory periods were an average of 2.44 +/- 1.04 msec (mean +/- SD) less than during drive from a single ectopic site (P less than 0.005). When fusion of activation, induced by ectopic and test site drive, was located within 4 mm or less of the test site, refractory periods during fusion drive were also significantly shorter than during test site drive (P less than 0.05). Refractory periods were as much as 10 msec shorter when fusion occurred within 1 mm of the test site than their durations during test site drive. The differences in refractory periods measured during various driving modes were most likely due to electrotonic interactions during ventricular repolarization and are explicable on the basis of the intracellular distribution of potentials to be expected with each driving mode.


Diet and sire effects on serum cholesterol and cholesterol absorption in infant baboons (Papio cynocephalus). One hundred three baboon infants, the progeny of an equal number of dams and seven sires, were breast fed or were fed prepared formulas containing 1.2, 29, or 61 mg/dl cholesterol for 14 weeks. We measured serum cholesterol and triglyceride concentrations at birth and at 3-week intervals, and cholesterol absorption at 12 weeks. Dietary cholesterol had a significant effect on serum cholesterol concentration at 12 weeks and on cholesterol absorption, but did not affect weight or serum triglyceride concentration. Sire had a significant effect on serum cholesterol concentration at birth and at 12 weeks, but the effect at birth did not predict the effect at 12 weeks. Sire did not affect cholesterol absorption, serum triglyceride concentration, or weight at 12 weeks. The sire effect on serum cholesterol concentration in infancy is not mediated by control of cholesterol absorption. Males weighed more than females at 12 weeks, but sex did not affect serum cholesterol concentration, triglyceride concentration, or cholesterol absorption.


Effects of nifedipine on myocardial perfusion and ischemic injury in dogs. To determine whether nifedipine, a calcium antagonist, protects ischemic myocardium, conscious dogs were subjected to coronary occlusion and given nifedipine by intravenous infusion beginning 30 minutes after the onset of ischemia and lasting for 24 hours while systemic arterial pressure, left atrial pressure, and cardiac output were monitored. Local myocardial perfusion at selected intervals after coronary occlusion was assessed with radioactive microspheres injected into the left atrium. In regions of myocardium exhibiting moderately depressed flow 29 minutes after occlusion in control dogs (n = 8), flow was significantly greater 3 and 23.5 hours later, reflecting increases in collateral perfusion. Corresponding zones of myocardium in treated dogs (n = 9) exhibited significantly greater increases in flow at each interval after occlusion (P less than 0.05). Furthermore, myocardial creatine kinase depletion (which correlated well with morphometric estimates of necrosis) in myocardium matched for ischemia prior to treatment was 1.5 to 3 times less in treated than in control dogs (P less than 0.05). Thus, nifedipine produced sustained increases in collateral flow and reduced myocardial ischemic injury.


Adenosine production in the ischemic kidney. We conducted experiments to determine (1) tissue, blood, and urine levels of adenosine produced by the ischemic kidney under conditions of renal artery occlusion, and (2) the site(s) of production and release of adenosine by the kidney. Concentrations of adenosine, inosine, and hypoxanthine in the dog urine were found to increase after 2 minutes of renal artery occlusion as were concentrations of these metabolites in renal tissue after 10 minutes of renal artery occlusion. Renal venous plasma levels of inosine and hypoxanthine also were elevated after 3 minutes of arterial occlusion. In modified stop-flow experiments, adenosine appeared in the urine in a peak that corresponded most closely with proximal tubule fluid. 5'-Nucleotidase, the enzyme which catalyzes the dephosphorylation of 5'-AMP or 5'-IMP to adenosine or inosine, respectively, was found to be located primarily on the external membranes and mitochondria of proximal tubule cells, but not in distal tubule or collecting duct cells. Since adenosine has been demonstrated to elicit renal vasoconstriction and is produced by the ischemic kidney, it is suggested that adenosine may be involved in the mediation of postocclusion renal ischemia.


Surface reflections of cardiac excitation and the assessment of infarct volume in dogs. A comparison of methods. Ventricular depolarization was analyzed in intact dogs by simultaneously recording body surface potential maps, McFee axial vectorcardiograms, and a 5 X 4 lead precordial grid of QRS complexes. The purpose of this study was to compare the effectiveness of subtraction approaches, using the simultaneously acquired data. The totally closed chest approach avoided the problem of volume conductor alteration by thoracotomy. Infarct volume was calculated morphologically from measurements of serial ventricular sections. The maximal correlation with anatomic infarct size using the precordial QRS grid approach was 0.51, using cumulative difference data between 1 and 38 msec when the postinfarction grid was substracted from the preinfarction grid. A correlation coefficient of 0.80 was achieved using the numerically integrated data between 1 and 31 msec from the vectorcardiogram, and the body surface potential map achieved a correlation coefficient above 0.88 when the electrical difference of msec 16 was used. These data suggest that estimates of infarct size from selected surface reflections of the activation process are feasible if some sort of preinfarction control data are available. Caution must be exercised to avoid inclusion of electrical effects late in the activation process which contain contamination by highly variable alterations in the excitation sequence due to delayed conduction or alteration in conduction pathway in or near the infarct zone.


Effects of a cardiac glycoside on regional function, blood flow, and electrograms in conscious dogs with myocardial ischemia. We studied the effects of coronary occlusion and of subsequent ouabain administration on regional myocardial function, flow, and electrograms in 14 conscious dogs. Coronary occlusion resulted in a graded loss of regional function as reflected by measurements of segment length (SL), velocity of SL shortening and myocardial "work" from the normal to severely ischemic zones, along with graded flow (radioactive microsphere technique) reductions and graded elevation of the regional S-T segment. Ouabain, 20 microgram/kg, improved function in the normal zone, in which stroke shortening rose by 0.23 +/- 0.07 mm (mean +/- SE) and "work" rose by 30.2 +/- 9.5 mm Hg-mm. In moderately ischemic segments, stroke shortening rose by 0.60 +/- 0.05 mm and "work" rose by 58.1 +/- 6.1 mm Hg-mm. In the majority of severely ischemic segments, stroke shortening and "work" also increased; the average effect in all severely ischemic segments was an increase in stroke shortening of 0.35 +/- 0.10 mm and in "work" of 31.5 +/- 9.9 mm Hg-mm. In addition, ouabain reduced S-T elevation by 0.90 +/- 0.20 mV in moderately ischemic zones and by 3.14 +/- 0.35 mV in severely ischemic zones, and increased flow by 28 +/- 6% and 46 +/- 9% in moderately and severely ischemic zones, respectively. All these changes were significant, P less than 0.01. Thus, ouabain caused an improvement in perfusion of ischemic tissue, which was associated with significant enhancement of stroke shortening and "work." Most strikingly, ouabain returned normal systolic shortening to 10 severely ischemic segments which previously were akinetic.