Lymphoma of the spinal extradural space. Ninety-four patients with lymphoma involving the extradural space with spinal cord compression proven at the time of laminectomy were reviewed. There were about three times as many patients with non-Hodgkin's lymphoma than with Hodgkin's disease. The majority of those with Hodgkin's disease had a proven histologic diagnosis before the onset of the spinal cord compression syndrome, whereas only 15% of those with non-Hodgkin's lymphoma had previously been so diagnosed. Plain roentgenograms of the spine were suggestive of tumor involvement in less than one-third of the patients, whereas myelograms were invariably abnormal. As noted by others, the outlook for functional recovery and extended life expectancy is relatively good for patients with this type of cancer, in contrast to reports in the literature regarding prognosis for patients who have metastatic carcinoma with extradural spinal cord compression.


Hodgkin's disease and chronic renal failure. A case of uremia resulting from bilateral Hodgkin's lymphomatous infiltration of kidneys is reported. Uremia was an initial feature in the case and was the eventual cause of death.


Chromosome studies in "preleukemia". III. Myelofibrosis. Cytogenetic studies were done on 18 patients with myelofibrosis or the closely related syndrome, undifferentiated myeloproliferative disorder (MPD). Clones of cells with chromosome abnormalities were demonstrated in the blood of eight individuals, including two with a history of radiation therapy and two with "acute myelofibrosis". Trisomy 8 was present in the latter two patients, but otherwise, there was no consistent cytogenetic pattern or correlation with specific hematologic findings. Sixteen of these patients have been followed for more than 1 year or until death; none has progressed to leukemia. The results indicate that chromosome abnormalities are relatively common in this disorder, but as with polycythemia vera, and unlike some other "preleukemic" states, the aberrant clones in myelofibrosis do not appear to indicate that clinical leukemia is imminent.


Combination chemotherapy for metastatic breast carcinoma. Prospective comparison of multiple drug therapy with L-phenylalanine mustard. A prospective randomized clinical trial was undertaken in 184 patients with metastatic breast carcinoma to compare single drug chemotherapy with L-phenylalanine mustard (L-PAM) and intermittent combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluourouracil (CMF). All patients had not been previously treated with cytotoxic drugs and all had objectively measurable visceral of soft tissue disease. Of the 93 patients who received CMF, 49 (53%) achieved a complete (14 patients) or partial (35 patients) regression of measurable tumor, for a median duration of 25 weeks. Eighteen of the 91 patients (20%) treated with L-PAM responded, for a median duration of 13 weeks. The toxicity was primarily hematologic, and greater in the CMF group, which also received more cycles of therapy because of the higher rate and duration of response. The overall survival of CMF-treated patients was superior to that of the single drug group. The differences were even greater when the patients were subclassified according to the presence of liver involvement or nonambulatory performance status. The superior antitumor effect of CMF over L-PAM suggests that it may be a more effective drug regimen to be used as an adjuvant to primary therapy.


Therapeutic trial of aniline mustard in patients with advanced cancer. Comparison of therapeutic response with cytochemical assessment of tumor cell beta-glucuronidase activity. Seventy-eight patients with advanced cancer received an adequate therapeutic trial with aniline mustard (NSC 18429). Significant anticancer activity with clinical benefit was demonstrated in five patients with cancer of the prostate and one patient with renal cancer. beta-glucuronidase levels in aspirate and imprint preparations of tumor cells were assessed by a timed cytochemical technique. A partial correlation appeared to exist between very intense glucuronidase staining and tumor regression in prostate and kidney lesions; however, these high levels were observed only rarely. Sequential observations in two patients demonstrated loss of enzymatic activity concomitant with development of clinical relapse.


Amphotericin B plus 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU-NSC no. 409962) in advanced cancer. Phase I and preliminary phase II results. Twenty-one patients with advanced metastatic cancer received amphotericin B (AmB) plus BNUC in a Phase I chemotherapy trial. Of 11 patients with measurable metastases from bronchogenic carcinoma, five had partial antitumor responses lasting 1.5 to 12+ months, and one had objective improvement. Only two of six patients with other types of tumors had objective improvement of short duration. No consistent evidence of immunologic stimulation was observed in eight patients studied. These results suggest that amphotericin B may increase the therapeutic ratio of BCNU, and further trials of this new concept in chemotherapy of advanced tumors are in progress. The dose-limiting toxicity was myelosuppression, usually thrombocytopenia. No enhancement of BCNU toxicity by the addition of AmB was observed. The recommended dose for future studies is: AmB, 7.5 mg/m2 on day 1, 15 mg/m2 on day 1, 30 mg/m2 on days 3 and 4; plus BCNU, 250 mg/m3 on day 4. The regimen is repeated every 6 to 8 weeks.


Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy. Vincristine, actinomycin D, and cyclophosphamide (VAC) were administered to 14 patients with Ewing's sarcoma. The primary tumors were treated with radiation therapy and concurrent chemotherapy. Nine patients had no visible metastases at diagnosis: two died following the development of pulmonary metastases and the rest have been free of disease for periods varying from 4 months to 4 1/2 years following completion of treatment. This contrasts with a 27% survival in patients previously treated at this center with single agent chemotherapy. Five other patients had demonstrable metastases at diagnosis: VAC chemotherapy achieved complete regression of pulmonary metastases in three for 9, 9+ and 24+ months, respectively. Following disappearance of tumor in the latter two, pulmonary irradiation was administered in an attempt to consolidate the response, but tumor recurred 6 months later. These patients eventually died of widespread disease although survival appeared prolonged in comparison to that seen in past experience. Chemotherapy was well tolerated, although three patients developed hemorrhagic cystitis, necessitating discontinuation of cyclophosphamide. The data suggest the potential for prolonged control and an increase in the cure rate with this therapeutic approach.


Criteria for obtaining and interpreting breast thermagrams. The thermal and graphic criteria which should be used to evaluate breast thermograms are outlined. Thermograms are then categorized as normal, suspicious, or abnormal on the basis of the criteria outlined. It is hoped that these criteria can be used widely to standardize breast thermographic evaluation.


Meningioma following irradiation.

Meningioma following irradiation. The case of a young woman who developed initial symptoms of an intracranial mass lesion 17 years after undergoing irradiation for a port-wine stain of the right fronto-temporal and periorbital scalp and face is reported. A right sphenoid wing meningioma was removed 6 years later. The possible relationship betweenthe development of the meningioma and the previous radiotherapy is discussed.


Nonspecific lymphocyte cytotoxicity in patients with malignant melanoma, renal cell carcinoma, and sarcomas, and in nontumor patients. Mononuclear cell-mediated tumor cell destruction was studied in 114 patients with malignant melanoma, renal cell carcinoma, or sarcomas, and in 122 non-tumor-bearing control subjects, with the use of the microcytoxicity assay. Cytotoxic reactions were found in all patients and control groups against melanoma, renal carcinoma, sarcoma, and fibroblast-derived cell cultures; mean levels of cytotoxicity against allogeneic combinations of tumor cells and fibroblasts were similar in tumor-bearing and control patients. These results support the concept that the reactions found represent nonspecific cytotoxicity.


Eosinophilic granular ceels in oligodendrogliomas. An ultrastructural study. In three cases of oligodendrogliomas, atypical cells rich in eosinophilic cytoplasm, resembling plump astroyctic or astroblastic cells, were studied under the electron microscopy. These cells showed finely granular cytoplasm with routine hematoxylin-eosin preparation; ultrastructurally, they exhibited abundant, round cytoplasmic bodies of autophagic-vacuole type, in addition to other fine structures characteristic of oligodendroglioma cells.


Light microscopic and ultrastructural observations of a metastasizing malignant epithelioid schwannoma. The light microscopy and ultrastructure of a malignant epithelioid schwannoma are described. Characteristic cells resembling perineural elements with various degrees of differentiation were observed. Primitive epithelioid cells contained scant ergastoplasm, and few tubules and filaments, but did have abundant free ribosomes and Golgi membranes. Also noted were junctional complexes and focal fusion of plasma membranes, basal laminae were absent. Better differentiated cells were completely limited by a well-developed basal membrane and had an abundance of intracytoplasmic filaments and multiple pinocytotic vesicles. The intercellular ground substance was composed of numerous fine collagen fibrils and amorphous, basement membrane-like, electron-dense material. A striking ultrastructural similarity of the tumor cells to those encountered in ethylnitrosourea-induced malignant schwannomas in rats was noteworthy.


Increased tetraploidy: cell-specific for the Gardner gene in the cultured cell. Human hereditary tumors in vivo are known to show tissue specificity. Increased endoreduplication with tetraploidy has been shown to occur in cultures established only from tissue containing epithelium (skin and colonic polyps) from patients with the Gardner syndrome. Cultures established from blood (short-term lymphocyte and lymphoid suspension) and connective tissue (subcutaneous tissue, lipoma, mesentery, and sebaceous cyst) from the same patients did not show increased tetraploidy. These observations demonstrated that tetraploidy as an expression of the gene for the Gardner syndrome was cell-specific in vitro and added further evidence that increased tetraploidy could be used for detection of the Gardner gene in families at risk.


Mixed ovarian tumor composed of Brenner and thyroid elements. An exceedingly rare ovarian neoplasm composed of mixed thyroid and Brenner tumor is reported. Review of the literature yielded only one well-documented case previously described. Although the possibility of a "collision" of two different tumors cannot be completely discarded, a possibility of an endodermal teratoma (thyroid-urothelium) is also proposed.


Squamous cell carcinoma originating in an hepatic cyst. Case report with a review of the hepatic cyst-carcinoma association. A case of squamous cell carcinoma originating in an hepatic cyst is presented. A review of the literature reveals five other cases of carcinoma arising within congenital intrahepatic cysts; three adenocarcinomas and two squamous cell carcinomas. Neoplastic transformation may also be seen in association with Meyenburg complexes, considered by some to be the structures from which congenital cysts arise.


Pulmonary carcinoid tumors is tissue and organ culture. Pulmonary carcinoid tumors arise from cells whose function is yet to be defined. Conditions for maintenance of cells of these tumors for prolonged periods of time in tissue and organ cultures were established in order to gain insight into their supposed endocrine activity. We succeeded in growing explants of these tumors in organ culture for as long as 5 months without the cells losing their ability to produce large numbers of neurosecretory-type granules.


Malignant skin tumors of neural crest origin. In a series of 90,000 consecutive surgical biopsies, ten malignant skin tumors were found that revealed at least two of three tissue components known to be derivatives of the neural crest, namely melanotic cells, neuroid structures, and chondrified tissue. The material studied supports a hypothesis presented earlier, that in spite of their morphologic variegation, such tumors from an entity defined by their common origin, the neural crest.


Familial Hodgkin's disease and associated cancer. A clinical-pathologic study. The etiology of Hodgkin's disease is complex, as is evident in studies suggesting the importance of horizontal transmission, occupational factors, racial and ethnic background, and familial, genetic factors, or both, including HL-A associations. The present study is of a remarkable kindred in which Hodgkin's disease was histologically verified in two sibships involving second-cousins related through maternal great-grandparents. Cancer of the lung, breast, endometrium, ovary, pancreas, and brain, as well as leukemia and Wilms' tumor, occurred in first and second-degree relatives of the Hodgkin's patients. HL-A haplotypes in patients with Hodgkin's disease in this family showed HL-AB5 or HL-ABW35, an association confirmed in other reports. The findings of associated malignant neoplasms in familial Hodgkin's disease, here and elsewhere in the literature, suggest that in the quest for etiology of Hodgkin's disease one must view the disorder eclectically, with a painstaking search for multiple etiologies, genetic and environmental.


Prostatic carcinoma. Correlation of histologic features of prognostic value with cytomorphology. Positive aspiration smears of 34 cases of histogically confirmed prostatic carcinoma were studied. Four features found to be of prognostic value in histologic material in a previous study--cell borders, lymphocytic infiltration, pleomorphism, and histologic typing of the tumor--were compared with the cytologic pattern present on the smears. Pleomorphism was the only feature for which good correlation was obtained between these two techniques. Unfortunately, the grade of pleomorphism is not reproducible from one observer to another. Cell borders, when present in groups of malignant cells in the smears, were also present in the sections. The absence of this feature in the smears did not imply absence in the sections.


Prostatic biopsy. A morphologic correlation of aspiration cytology with needle biopsy histology. One hundred and eighteen aspiration biopsies of the prostate are correlated with needle biopsies. The overall accuracy of the needle biospy is 85.6% and that of the aspirates is 86.6%. The author recommends that both techniques should be used simultaneously in the diagnosis of carcinoma of the prostate. Descriptions are given of benign and malignant cell types in prostatic aspirates, with special emphasis on the features differentiating benign atypia of prostatic cells from well-differentiated adenocarcinoma, as this is potentially an important source of false-positive reports in aspiration smears.


Polyamines in malignant melanoma. Urinary excretion and disease progress. Urinary polyamine concentrations in 91 samples were assayed in 79 patients with malignant melanoma who were classified as to clinical stage, as well as to activity of disease. Patients with active disease had higher mean polyamine values, increased frequency of polyamine elevations, and increased frequency of two or more elevations, than did patients with stable disease. Elevations of a single polyamine were seen as frequently in patients whose disease was considered stable as in those who showed progression. The polyamines may be useful as guides to activity of the disease, provided further studies can identify additional sources of nonspecific elevations.


Metastatic uterine leiomyomata. A case report. Pulmonary metastases from uterine leiomyomata are extremely rare and unpredictable, despite the high frequency of uterine leiomyoma. Review of the literature reveals seven previous examples of pulmonary metastasis from uterine leiomyomata; other cases may exist, but they were not considered because there was little evidence to distinguish them from leiomyosarcoma. The case we report is unusual in: 1) its prolonged course of 21 years, 2) its lack of pulmonary symptoms, despite extensive multiple nodules; and 3) the cystic change of the multiple lesions, which mimicked cystic lung disease.


Plasma estrogen in patients with endometrial hyperplasia and carcinoma. In a total of 53 patients, most of whom were over 40 years of age and who presented symptoms of vaginal bleeding, total plasma estrogens were measured with gas liquid chromatography, and the clinical correlates were studied. The results revealed that total plasma estrogen levels in the endometrial hyperplasia and endometrial carcinoma groups were significantly higher than those measured in the control group. In addition, a positive, significant correlation was found between the plasma estrogen levels and obesity in the patients with endometrial carcinoma. The study provides objective data that document the clinical impressions that hyperestrogenism and obesity are significant findings in endometrial carcinoma.


Pulmonary tumor emboli and cor pulmonale in primary carcinoma of the lung. Tumor embolization was found at autopsy in the pulmonary arteries of 33 of 331 patients dying with primary carcinoma of the lung (other than oat cell carcinoma). Venous or lymphatic vascular involvement, or both, was greater frequency of tumor embolization htan epidermoid carcinomas (16.5% vs. 5.8%). In 16 of the 33 cases, diffuse, obliterative intimal fibrosis was found in small arteries affected by the tumor embolization. Enlargement of the right cardiac ventricle was present in 26 of the 33 cases. Dyspnea as the initial symptom or as one of the major symptoms, occurred in 21 patients. The average interval between onset of dyspnea and death was 4 weeks. It is concluded that pulmonary arterial embolization is a relatively frequent complication of primary lung carcinoma, particularly adenocarcinoma, which may lead to the developemnt of pulmonary hypertension and cor pulmonale Dyspnea, occurring de novo in patients with primary lung carcinoma is an ominous sign and should alert the clinician to the possibility of arterial pulmonary tumor embolization.


Unusual isomaylase in cancer-associated hyperamylasemia. Hyperamylasemia and hyperamylasuria were found in two patients with carcinoma of the pancreas and in two other patients with carcinoma of the lung. Detailed isoamylase analyses were conducted on the serum amylase of three and the urine amylase of all four of these patients, using a modified chromatographic procedure. The studies demonstrated the existence, in one of the lung cancer patients and in one of the patients with pancreatic cancer, of an unusual component of amylase given the designation "Y." This component had also been noted in some human milk samples. In one of the lung cancer patients, an isoamylase was found in the serum and urine after radiation treatment that was close to but not identical to the Y isoamylase in chromatographic position. Although a relationship of isoamylase component Y to generating tissue is suggested by these findings, such a relationship of isoamylase component Y to generating tissue is suggested by these findings, such a relationship remains to be proven.


Alterations in plasma sialyltransferase associated with successful chemotherapy of a disseminated tumor. Case report. Levels of plasma sialyltransferase were measured in a  patient with disseminated carcinoma of the testes. Initial enzyme values, elevated six fold above those in normal controls, were among the highest thus far encountered in a population of patients with various stages and types of malignancy. During a remarkable respose to chemotherapy with cis-diaminodichloroplatinum, plasma sialyltransferase levels fell markedly. Serial measurement of this enzyme may aid in evaluation of tumor responsiveness to therapy in patients whose disease is not readily measurable.


Neoplasms of the central nervous system. incidence and population selectivity in the Washington DC, metropolitan area. During the period 1960 through 1969, 990 primary neoplasms of the central nervous system were diagnosed in hospitals in the Washington, DC, Standard Metropolitan Statistical Area (SMSA). All cases were identified according to age, race, sex, histologic type, and date of diagnosis. A West African composite of 253 cases was used for comparison. In the Washington SMSA, the age-adjusted incidence rates were: for Caucasians 5.5 in males and 3.6 in females and for Negroes 4.8 in males and 3.4 in females per 100,000 annual population. Caucasians in the Washington SMSA had a higher relative proportion of gliomas than Negroes in the same area and in Africa (p less than 0.005). The relative proportion of pituitary adenomas was higher in American Negroes (p less than 0.005) and in Africans than in Caucasians. The comparable pattern of CNS tumors in American and African Negroes, relative to Caucasians, suggests that in the development of neoplasms of the central nervous system racial factors may be of importance.


The ultrasonographic spectrum of abdominal and pelvic Hodgkin's disease and non-Hodgkin's lymphoma. Diagnostic B-scan ultrasonography has the capacity to evaluate many potential sites of abdominal and pelvic involvement by Hodgkin's disease and non-Hodgkin's lymphoma. The varying ultrasonographic features of lymphomatous involvement in the peritoneal cavity and retroperitoneal space are described and potential diagnostic pitfalls are discussed.


Leptomeningeal mycosis fungoides.

Leptomeningeal mycosis fungoides. Central nervous system involvement with mycosis fungoides complicated the clinical course of a patient at a time when his skin was clinically free of disease following systemic chemotherapy. A leptomeningeal syndrome of blurred vision and papilledema, and confusion progressing to coma, was associated with elevated spinal fluid pressure and abnormal spinal fluid cells morphologically similar to those seen in the Sezary syndrome. The symptoms were dramatically reversed by intrathecal methotrexate, brain irradiation, and steroids. Mycosis fungoides recurred in the skin, in the spinal fluid, and in both eyes. Despite continued systemic and intrathecal chemotherapy, the patient died from mycosis fungoides. This is the second patient reported with meningeal mycosis fungoides.


Leiomyomata of the esophagus. An analysis of 838 cases. Review of the world literature to the end of 1971 has provided data on 838 cases of esophageal leiomyomata, including our own 19 surgically removed lesions. Although esophageal leiomyoma is the most common of the benign tumors of the esophagus, it is still rare compared with carcinoma. It occurs in more men than women, by a ratio of 1.9 to 1. Over 50% of the patients with leiomyoma of the esophagus are asymptomatic. Dysphagia and vague pain are the most frequent symptoms. Pyrosis is mentioned in the literature as present in 40% of the cases, but it is considered mainly as symptom of coexistent hiatal hernia. Diagnostic problems often arise, as the smooth muscle tumors may mimic mediastinal neoplasms, cysts, or even aneurysms, or complicate coexisting hiatal hernia and esophageal diverticulum. Operative management by transthoracic enucleation is the procedure of choice, although resection of the esophagaus may be required in few cases. Postoperative morbidity is minimal and results are excellent.


Recurrent urothelial tumors following surgery for transitional cell carcinoma of the upper urinary tract. A retrospective analysis of 74 cases of transitional cell carcinoma of the renal pelvis and ureter treated at this institution over the past 30 years is presented. When nephrectomy alone or incomplete nephroureterectomy was performed, subsequent transitional cell carcinoma developed in 30% of the ureteral stumps. Subsequent bladder carcinoma occurred in 25% of the patients with primary upper urinary tract carcinoma. The type of initial surgery performed did not appear to influence this incidence of subsequent bladder tumors. Contralateral upper urinary tract carcinoma developed in only one patient. When nephroureterectomy is performed for carcinoma of the renal pelvis and ureter, a cuff of bladder that includes the ureteral orifice should be removed to obviate recurrent disease in the ureteral stump. Since single-incision nephroureterectomy did not include the intramural ureter in 50% of the cases in which it was performed, a second incision may be required for adequate exposure.


Psychological response of patients cured of advanced cancer. Psychologic testing was performed in 22 patients with advanced cancer (breast, endometrium, testis, lymphoma) who had undergone a complete remission that had been maintained for 5 to 20 years since the last therapy. The reaction to the probability of being cured was measured. The patients' overall attitude was very positive towards life and the future. They had a greater appreciation of time, life, people, and interpersonal reactions. They were less concerned about the nonessentials of life. It appeared that recovery from advanced cancer was a good experience for character development.


Sudden death.

Sudden death. The threat of sudden death due to a myocardial infarct inevitably places a severe strain on the patient, who may realize the severity of his condition, on the family who are justifiably concerned about the life threatening situation the patient is in, and on the coronary care nurse who is involved in his care. Each one reacts to this stress in his own way. If the nurse can begin to understand her own reactions and the reactions of the family and patient, she will be better equipped to help them cope with this crisis situation.


Home care after surgery for scoliosis.

Home care after surgery for scoliosis. Parents are normally highly motivated to learn how to give care to their children. Adolescents convalescing after Harrington instrumentation and spinal fusion need to actively participate in decisions concerning their care. As much effort as possible should be made to allow them to follow a normal routine, within the limits of the surgeon's instructions. Both parents and patients need teaching, support and reinforcement from the nurse. They need to know how they are coping. The parents need to be supported and reinforced in their performance of home care and in their acceptance of the patient within the family life-style. Adolescents need to be supported in their independence and adjustment to their new and temporary immobility. Assessment of the home and an informative teaching program on home care needs to be initiated as soon as possible after surgery.


The identification and treatment of "difficult" babies. The "difficult" baby can grow into the difficult child unless the early signs of behavior disruption are identified and treated. The best person to spot these warning signals and to aid and educate the new mother in techniques for overcoming them is the public health nurse. In her home visits and pre-and postnatal classes she is the key figure in an important preventive exercise.


Towards independence for paraplegics.

Towards independence for paraplegics. Good rehabilitation emphasizes the abilities rather than the disabilities of the paraplegic and promotes the greatest level of self-care and independence possible. However, even with a level of independence, there still exist societal barriers that prevent the disabled from assuming a greater involvement in the community. Educating the government and the public, about the need for more and better suitable housing, more vocational opportunities, fewer physical barriers such as high curbs, stairs and narrow doorways that prevent access to public and commercial buildings and trying to encourage positive attitudes toward the disabled will help bring the paraplegic out of isolation and allow him to develop a full, active life.


The market for nurses - we've come a long way. The oldest and largest segment of nursing manpower is the diploma educated R.N. This year, several thousand R.N.'s across the country are actively seeking work and are unable to find it. Many of these unemployed nurses are in the province of Ontario. A look at the Ontario experience in the area of nursing manpower offers some interesting insights into developments in other provinces and territories.


Modulating effects of levamisole (NSC-177023) on human lymphocyte response in vitro. Human lymphocytes were cultured in vitro with multiple concentrations of antigen, mitogen, and allogeneic cells. The addition of levamisole to stimulated cultures in concentrations of 0.03-33 mug/ml significantly amplified the response of lymphocytes to these stimuli with little or no effect on control cultures. The combination of stimulus and levamisole concentration which produced amplification was unique for each individual culture. The inconsistent results found here and elsewhere may reflect instability of levamisole under conditions of the in vitro lymphocyte culture system.


Trial of heparin and cyclophosphamide (NSC-26271) in the treatment of lung cancer. Preliminary reports have suggested that heparin may enhance the effectiveness of chemotherapy for lung cancer. The VALCSG initiated a study to evaluate further the efficacy and feasibility of administering a heparin and chemotherapy regimen. Treatment consisted of continuous iv heparin infusion for 48--72 hours followed by iv administration of cyclophosphamide (1100 mg/m2) and continued treatment with heparin and warfarin. Only one of the 19 patients (5%) with nonresectable or metastatic lung cancer showed evidence of objective tumor response. This indicated no benefit from the addition of heparin. The study also revealed some of the limitations and problems of such a treatment program.


Study of in vivo tumor state and response to therapy by analysis of DNA distribution. The growth characteristics of an in vivo tumor model were studied. This tumor offers an intermediate system useful for the study of tumor cells in the intact animal, but does not have the complexities of solid tumors. DNA distribution was correlated with macromolecular DNA synthesis. Mechlorethamine, BCNU, radiation, and hydroxyurea were studied and produced perturbation in stationary phase-cell kinetics. There was a redistribution of cell ages consistent with induced cycling activity with most, but not all, of the above agents. This indicated a recruitment from a stationary phase by cancer therapeutic agents, although subsequent cell-cycle traverse may also be greatly perturbed. A number of considerations important to the interpretation of this type of data are discussed.


Maintenance of remission in adult acute nonlymphoblastic leukemia using intermittent courses of cytosine arabinoside (NSC-63878) and 6-thioguanine (NSC-752). Twenty adults (median age, 58 yrs) with acute nonlymphoblastic leukemia who had achieved complete remission were given maintenance therapy with monthly courses of cytosine arabinoside and 6-thioguanine, each in a dose of 100 mg/m2 every 12 hours for ten doses. The toxicity was minimal with no severe infections, bleeding, or treatment-related deaths. The treatment was often administered on an outpatient basis. The predicted life-table median remission duration is 14 months with 11 patients still in remission from 3+ to 29+ months.


Study of cytosine arabinoside (NSC-63878) synchronization plus vincristine (NSC-67574), prednisone (NSC-10023), and L-asparaginase (NSC-109229) for remission induction in advanced acute leukemia in children. Cytosine arabinoside (CA) was utilized in efforts to synchronize leukemic cells in DNA synthesis for treatment with vincristine, prednisone, and L-asparaginase in children with acute leukemia in relapse. The results did not indicate any therapeutic advantage for patients treated with this combination compared to those treated without any attempt at CA synchronization.


DTIC (nsc-45388) and combination therapy for melanoma. I. Studies with DTIC, BCNU (NSC-409962), CCNU (NSC-79037), vincristine (NSC-67574), and hydroxyurea (NSC-32065). A total of 270 patients with metastatic malignant melanoma were entered into a randomized chemotherapy study conducted by the Central Oncology Group (COG) over a period of 2 years (COG protocol No. 7130). The study utilized DTIC, CCNU, BCNU, vincristine, and hydroxyurea. The results of therapy with DTIC alone were compared with three combinations: (a) DTIC, CCNU, and vincristine; (b) DTIC, BCNU, and vincristine: and (c) DTIC, BCNU, and hydroxyurea. There were 243 evaluable patients out of 270. The response rate was 17.3% (42 of 243 patients) for evaluable patients and 15.5% (42 of 270 patients) for all patients entered in the study. The results showed no statistically significant difference in the response rates among the four treatment arms. However, several significant points were observed: (a) A 13% response rate was obtained using a combination of agents that included DTIC in patients who had previously shown no response to DTIC used as a single agent. (b) There was a significant difference in survival time when comparing responders to those with no change and to those with progression. (c) Toxicity was noted to be greater in responders than in nonresponders. (d) Two of the four treatment arms were considered most advantageous due to the ease of administration. These treatment arms were DTIC, BCNU, and vincristine and DTIC, CCNU, and vincristine administered in 5-day courses every 6 weeks. (e) The percentage of response and length of survival were significantly greater in patients without brain or liver metastasis. (f) In comparing men to women there was no statistically significant difference in response in rates or durations of response. (g) There was no statistically significant difference in survival when comparing site of primary lesion.


Phase I evaluation of dianhydrogalactitol (NSC-132313). A toxicologic evaluation of dianhydrogalactitol in man was completed for a 5- and a 10-day schedule. The maximum tolerated dose was 30 mg/m2/day for the 5-day schedule and 21 mg/m2/day for the 10-day schedule. Dose-limiting myelosuppression occurred with both schedules, with leukopenia and thrombocytopenia being observed at median Days 15 and 19 respectively for the 5-day course and median Days 22 and 26 of the 10-day course. Nausea was infrequent and mild. Responses were obtained in one patient with laryngeal carcinoma and in one patient with adenocarcinoma of the lung.


Isolation and chemical characterization of antitumor agents from plants. This paper reviews methods which have evolved at the Research Triangle Institute during the last 15 years for the isolation and characterization of antitumor agents from plants. The isolation procedures stress mild, nonchemical methods. Solvent partition and the Craig Counter Current Distribution are used during the early stages of fractionation. Subsequent purification involves many types of chromatography: adsorption, partition, thin-layer, preparative thin layer, gel-exclusion, and medium- and high-pressure liquid chromatography. The pure compound is crystallized from a suitable solvent. The fractionation is monitored with in vitro and in vivo bioassays. Physical methods used for structure determination are: ultraviolet, infrared, and nuclear magnetic resonance spectrometry, and X-ray crystallography.


Preparation of plant extracts for antitumor screening. Random collections of plants have been screened by the National Cancer Institute's screening program for almost two decades. The WARF Institute, Inc. (Madison, Wis) has been preparing most of the crude plant extracts for antitumor screening for the past 14 years. This paper describes our present method of extraction for preparation of crude plant extracts for screening and presents a history of past procedures used for the extraction of plant materials. Wherever possible, screening statistics have been included for plants which have been extracted by the various procedures.


Polarized infrared spectra of crystalline glycosaminoglycans. Polarized infrared spectra have been recorded for oriented, crystalline specimens of hyaluronates, chondroitin 4-sulfate and 6-sulfate, dermatan sulfate, and a cartilage proteoglycan, having different known chain conformations as determined by X-ray diffraction. The dichroism data for the vibrational modes of the amide and carboxyl groups have been interpreted with respect to the particular molecular structures.


Magnetic, immobilised derivatives of enzymes. A novel, water, insoluble, stable coating has been attached to various metals, which is capable of covalent attachment to enzymes. The coating (aminobenzoic acid-formaldehyde resin) can be attached to nickel, cobalt, tin, iron, and aluminium. beta-D-Glucosidase has been attached to the coated metals by diazotisation of the coating. The stability and usefulness of the resulting, metallic enzyme-preparations is discussed with special emphasis on the value of ferromagnetic supports for enzymes.


Cardiovascular action of verapamil in the dog with particular reference to myocardial contractility and atrioventricular conduction. Verapamil (Isoptin) caused a dose-dependent peripheral vasodilation, increase in myocardial contractility, and tachycardia in the anaesthetized dog. Propranolol pretreatment blocked the cardiac stimulation following verapamil but the vasodilation was unaltered. Inflation of a thoracic aortic balloon prevented the fall in intravascular pressure and reduced the tachycardia and positive inotropic responses. These experiments suggest that clinical doses of verapamil cause peripheral vasodilation which leads to a sympathetic reflex induced increase in heart rate and myocardial contractility. Verapamil also had a direct myocardial depressant action which became evident at doses above the range used clinically. The drug increased the PR interval in conscious dogs for up to 60 minutes. This effect was partly mediated through cholinergic stimulation and partly through a direct depression on atrioventricular conduction.


Myocardial oxygen consumption after major coronary artery occlusion in anaesthetized dogs with constant left ventricular workload. In dog preparations with fixed external workload, reduction of functioning myocardium from 13.3 to 40.9 degrees by coronary artery occlusion (CAO) did not affect myocardial oxygen consumption for periods up to 77 min following CAO. Thus, the use of reserve capacity supplementing equal functional loss of myocardium does not alter oxygen consumption.


A protective effect of verapamil on hypoxic heart muscle. Hypoxic-induced damage of rabbit heart muscle has been quantitated in terms of the release of intracellular enzymes (including creating phosphokinase, CPK) into the extracellular space, a gain in tissue Na+ and Ca2+, a loss of tissue K+, the depletion of the adenosine triphosphate (ATP) and creatine phosphate (CP) reserves, and ultrastructural damage. This ultrastructural damage incolves the disruption of the plasmalemma, swelling and distortion of the mitochondria, disruption of the myofilaments, and the development of contraction bands. In isolated Langendorff-perfused rabbit hearts perfused under either aerobie (pO2 greater than 80.0 kPa [600 mm Hg]) or hypoxie (pO2 less than 0.80 kPa [6 mmHg]) conditions, and either with or without glucose substrate, 0.5-1.0 mg/litre dl verapamil reduced the amount of ultrastructural damage caused by hypoxie perfusion. Verapamil (0.5-1.0 mg/litre) also reduced the rate at which the hypoxie muscle gained Na+ and lost K+; it reduced the rate at which the endogenous stores of ATP and CP were depleted and, provided that the extracellular phase contained Ca2+, it decreased the rate at which CPK appeared in the coronary effluent. Verapamil failed to prevent the hypoxie muscle from gaining Ca2+. These results are discussed in terms of a possible protective effect of dl verapamil on hypoxie heart muscle.


Influence of inflation and atelectasis on the hypoxic pressor response in isolated dog lung lobes. Apnoeic left lower lobes of dog lungs were inflated by increasing alveolar pressure or decreasing pleural pressure, or the lobes were collapsed and exposed to decreasing pleural pressure with the bronchus occluded. Under each of these conditions the lobe could be made 'hypoxic' by perfusion with mixed venous blood or 'normoxic' by perfusion with systemic arterial blood. Inflation of the lobes diminished the hypoxic presor response. The relative influence of decreasing pleural pressure on inflated and collapsed lobes was such that at low pleural pressures resistance to flow through the hypoxic atelectatic lobe was no greater than that through the inflated normoxic lobe. The results indicated that the level of lung inflation can alter the effectiveness of the hypoxic pressor response in reducing perfusion to underventilated regions.


Persistence of myocardial injury following brief periods of coronary occlusion. Transient (20 min) occlusion of the left anterior descending coronary artery in open-chest anaesthetized dogs caused immediate aneurysmal bulging of the ischaemic segment, which preceded epicardial ST-segment elevation. Reperfusion after 20 min restored epicardial electrograms to normal, wheras mechanical dysfunction persisted for a least 45 min therafter. The study shows that there is temporal disparity between electrical and mechanical events both at the inception of myocardial ischaemia and during recovery from transient myocardial ischaemia.


Effects of lignocaine on intramyocardial conduction in nonischaemic and ischaemic canine myocardium. The effect of lignocaine (USP: lidocaine) on intramyocardial conduction in ischaemic and nonischaemic areas of the left ventricular myocardium was determined in  11 mongrel dogs. Intramyocardial conduction times were assessed during control conditions, 15 min after coronary ligation, and following lignocaine administration. Coronary occlusion resulted in a disparity between the conduction velocities in the ischaemic and nonischaemic zones. Ater lignocaine administration conduction to the ischaemic area was further decreased. However, conduction to the nonischaemic area was decreased to a relatively greater extent, resulting in a significant decrease in the disparity of conduction velocities in the two areas. It is concluded (1) that lignocaine exerts dissimilar quantitative effects on the nonischaemic and acutely ischaemic myocardium and (2) that these differential effects decrease the inhomogeneity of intraventricular conduction. It is possible that this action may play a role in the suppression of re-entrant arrhythmias.


Cardiovascular responses in man to a stream of cold air. Cardiovascular responses to a stream of cold air (0-10degrees C) directed towards the face and abdomen separately were examined in 12 human subjects. Cold air directed at the side of the face produced a 36+/-6 degrees increase in forearm vascular resistance and 22"/-4 degrees reduction in blood flow. Cold air on the abdomen did not produce a significant change in vascular resistance. The results are discussed in relation to angina pectoris evoked by cold wind.


[Comparative morphological study of the prothallial development in Asplenium species]. This study concerns the comparative development of gametophytes of nine Asplenium species. Some of them are diploïd, others tetraploid. They were studied on a cytogenetic point of view by british workers who found parental relationships between these species. The morphological analysis of the gametophytic development permits to determine the definite stages on which the tetraploïd species like to the supposed diploid parents. The inherited morphological characteristics are also described, for instance: formation of the prothallial plate, form of the marginal hairs. This qualitative analysis of the gametophytic development is not sufficient to confirm the supposed parental relationships. Therefore, precisions are given by the results of the quantitative analysis of the prothallial development and the study of the vascularization of the young sporophytes; these results will be soon published.


[Quantitative study of the prothallial morphogenesis in Asplenium species]. A precedent paper concerned a qualitative analysis of the gametophytic development in nine Asplenium species. By a quantitative study, we specify the parental relationships among these species. The surface of the gametophyte and the number of maginal hairs increase differently for each species. The density of the marginal hairs depends on the considered species. The relation among the morphological gametophytic parameters is constant in a group of determined species. The principal componant analysis is realized for all the parameters measured during the prothallial development. It confirms parental relationships among the diploids and tetraploids species on a morphological point of vue.


[A cytotaxonomic study of Rumex. IV. The Acetosa Mill. species]. 1. Karyotypes of 18 species of the sections Scutati (2), Vesicarii (2), Hastati (4), Afroacetosae (2) and Acetosa (8) of the genus Acetosa have been investigated in detail. 2. Four evolutive tendancies were distinguished i.e.: decrease of chromosome number and arm ratio, increase of chromosome length and differentiation of sex crhomosomes. These tendancies are fully expressed in the section Acetosa as compared with the others. 3. In this section, relationships between the subsections Acetosa, Insectivalves and Americanae were established especially dealing with the change of sex determination from the type XX/XY to the type XX/XY1Y2. 4. Evolutive pathways within the genus Acetosa as well as in the whole group of Rumex sensu lato are described.


Freeze-etch and histochemical evidence for cycling in crayfish photoreceptor membranes. Freeze-etched rhabdoms and adjacent cytoplasmic cytoplasmic organelles from crayfish compound eyes have been studied for evidence of photoreceptor membrane cycling. The protoplasmic leaflet face (PF) of split photoreceptor membrane of the microvilli is richly particulate. The particles (92 +/- 16 A in diameter in surface fractures; 70 +/- 9 A in cross fractures; density about 8000/mum2) probably indicate rhodopsin molecule localization. Closely similar particles appear in membranes of pinocytotic vesicles, multivesicular bodies (MVB) and secondary lysosomes. In contrast other retinular cell membranes like plasma membrane remote from the rhabdom are quite distinct (60 +/- 23 A particle diameter, density ca 1000/mum2.) Histochemical tests for acid phosphatase demonstrate its presence in well-developed (but not early stage) MVBs, mixed lamellar vesicular bodies (LVB) and lamellar bodies. Density of PF particles decreases from 8000 in MVB to roughly 4500/mum2 in LVB indicating a degradative sequence from rhabdom to lamellar bodies. Membrane leaflet orientations show that primary endocytosis from microvilli must be followed by secondary endocytosis of fused coated vesicles to form MVB. Morphological evidence for photoreceptor membrane resynthesis has not been found yet in crayfish but some has been obtained in other crustaceans.


Polymorphism in the rotifer Asplanchna sieboldi. Fine structure of saccate, cruciform and campanulate females. The morphology of saccate, cruciform, and campanulate females of Asplanchna sieboldi was analyzed by light and electron microscopy. No major qualitative variations were observed in the ultrastructure of the hypodermis, gastric gland and yolk gland of females from the different morphotypes. Campanulate females did, however, possess larger secretory granules in their gastric gland as well as larger and more numerous nuclei in their gastric and yolk glands than both saccate and cruciform females. The structure of the secretory elements in the gastric gland varied between the two clones investigated.


Structure of cells and nerve endings in abdominal vagal paraganglia of the rat. The abdominal vagal paraganglia of the rat consist of small groups of cells, interspersed by blood vessels and nerve bundles and lying close to, or within, the vagus nerve or its branches. Each cell group consists of 2-10 Type I cells incompletely invested by 1-3 satellite cells. Type I cells are characterised by the presence of numerous dense-cored vesicles in their cytoplasm and may exhibit 'synaptic'-like contact with each other. Small efferent nerve endings make synaptic contacts with Type I cells. Larger cup-shaped afferent nerve endings also make synaptic contacts of two kinds with Type I cells. Nerve-nerve synapses are often seen within or close to paraganglia. Attention is drawn to the close similarity of fine structure of abdominal vagal paraganglia, carotid body and small intensely fluorescent cells of the superior cervical ganglion in rats. Possible functional implications of this morphological similarity are discussed.


Histological and ultrastructural studies of the rabbit pars intermedia in organ culture. I. Adult and young adult tissue. Fuuly differentiated rabbit pars intermedia has been maintained successfully for over six weeks as organ culture. PI-glandular cells are the commonest type throughout the culture. They retain their differential condition for at least five weeks. Autoradiography indicates that cell division occurs in cultures for at least two weeks. Dense granules are seen in the intercellular, perivascular and vascular spaces and are taken to indicate secretory activity under the conditions of culture. Some interstitial cells remain recognisable throughout the culture and ACT-type cells for more than two weeks. Other interstitial cells lose their usual appearance and become peripheral dark cells. Modification of cytoplasmic organelles, including distortion and darkening of mitochondria, increase in intracellular filaments and enlargement and liberation of the content of the PI-vesicles are reported.


Experimental study of changes in osteoblastic shape induced by calcitonin and parathyroid extract in an organ culture system. Neonate rat endocranial osteoblasts were cultured on their bone surfaces in control medium (CC) or medium to which either parathyroid extract (PTE) or calcitonin (CT) had been added for 2, 4, 8 or 24 h. Some were cultured for 24 h in CC, then for 2, 4, 8 or 24 h in either CT or PTE medium; or for 24 h in PTE, then for 2, 4, 8 or 24 h in either CC or CT; or 24 h in CT and 2, 4, 8 or 24 h in CC. The dorsal ruffling of the cells in CC was found to be suppressed by later culturing with PTE and the disoriented cells reorganized to form arrays of parallel cells. The effects of PTE were also reversed by CC or CT: the osteoblasts in the second culture (CC) lost elongation and order, and proceeded through a proliferative phase before exhibiting the ruffling form similar to a single CC 24 h culture. PTE-cultured osteoblasts showed an increase in cell overlap and contact so that a more competent barrier was formed separating the bone from the medium. In control or CT medium, however, intercellular gaps were greater than in vivo.


Structural changes occurring during atresia in sheep ovarian follicles. The structural changes that characterize primary, secondary and tertiary atresia in sheep Graafian follicles have been studied by means of histological, histochemical and ultrastructural techniques. In primary atresia vacuoles representing swollen endoplasmic reticulum are prominent along the antral border together with disorganized granulosa cells containing pyknotic nuclei. Phagocytic cells, which increase in number as atresia progresses, were seen within the membrana granulosa and are considered to be transformed granulosa cells. Even in follicles classified as nonatretic, a few antral vacuoles and occasional pyknotic nuclei are present. During secondary atresia there is a large increase in the number of cells with pyknotic nuclei; many of these nuclei had been extruded and had fused to form the characteristic Feulgen-positive atretic bodies found along the edge of the antral cavity. These bodies usually have a diameter of up to 15 mum but occasionally reached as much as 400 mum. A second area of degeneration is frequently present in the membrana granulosa, two or three cell layers from the basal lamina, and it is at this level that exfoliation of granulosa cells occurs in tertiary atresia. In contrast to the membrana granulosa, there are during secondary atresia, only slight indications of degeneration in the cumulus. In tertiary atresia the membrana granulosa is highly disorganized; the atretic bodies are often fewer in number than at earlier stages. The basal lamina remains essentially intact. It is at this stage that the first clear signs of degeneration occur in the theca interna. Despite some disintegration of the cumulus, the integrity of the oocyte is maintained and its nucleus remains vesicular. Changes in the thecal microcirculation may plan a key role in atresia: adjacent to the basal lamina of non-atretic follicles, there is a well-developed capillary network which is significantly reduced as atresia progresses.


Variations in mitochondrial size and ultrastructure during germ cell development. Size variations and ultrastructural changes in mitochondria of developing germ cells of the female hamster were analyzed. Mitochondria in oogonia of foetus and newborn were elongate with transverse cristae. During pre-dictyate meiotic prophase they became small, rounded, and electron-dense with pleomorphic cristae. These changes were largely reversed when dictyate was reached. Maximum mitochondrial size and complexity of cristae were reached just at the beginning of the phase of rapid oocyte growth, and thereafter declined. As mitochondrial size and number of cristae decreased in the rapidly enlarging oocyte, the ratio of length to width increased, as did electron density of the matrix, until the formation of an antrum within the follicle. After antrum formation, the mitochondria again became more rounded and cristae were seldom seen. An attempt is made to correlate changes of mitochondrial morphology with other events occurring during oogenesis.


Degenerated boutons in the fundus striati (nucleus accumbens septi) after lesion of the parafascicular nucleus in the cat. An attempt has been made to reveal which of the nine different types of synapses in the fundus striati, discriminated in a previous study, degenerate following experimental lesions in the parafasciculo-center median complex of the cat. Two types of synaptic contacts were found to be degenerated two days after the lesion was performed: (1) the axo-spinous type IV, characterized by densely-packed, small, round vesicles and a strong asymmetric thickening, and (2) the axo-dendritic or axo-somatic type VII, again characterized by small, round vesicles in a dense accumulation and an asymmetric thickening. After two days of survival the original characteristics of the boutons could still be recognized in both types of synapses. A positive correlation exists between the location and extent of the coagulation foci in the parafascicular nucleus and the appearance of degenerated boutons in the fundus striati. Therefore, the conclusion that the parafasciculofundus neurons terminate as type IV or type VII boutons is entirely justified. Additionally, the role of the special types of boutons in the synaptic organization of the fundus striati has been discussed.


The pyramidal cells of Betz within the cingulate and precentral gigantopyramidal field in the human brain. A Golgi and pigmentarchitectonic study. It can be demonstrated with the aid of Golgi-, Nissl-, and pigment preparations that the Betz cells represent a homogeneous class of giant cells within the human brain, which can readily be distinguished from other large pyramids by their densely aggregated lipofuscin deposits. In addition to the primary motor field (4, Brodmann), there exists only a small area on the medial surface of the hemisphere in front of the central sulcus which also contains large Betz pyramids in layer Vb. This recently discovered sulcus (Braak, 1976b). Compared with the Betz cells of the primary motor field (4, Brodmann), those of the cingulate area display numerous primitive traits. A small number of short basal dendrites springs off from the cell body. The apical dendrite forks in a short distance from the perikaryon repeatedly but issues only few side branches. A spine-free proximal dendritic segment is poorly developed or lacking. Moreover, numerous spines are encountered along the surface of the soma. In view of their primitive features the large pyramids of the cingulate gigantopyramidal area are interpreted as the forerunners of the precentral Betz pyramids.


Postnatal ontogenic development of the adrenergic innervation pattern in the rat portal vein. A histochemical study. The postnatal development of the adrenergic innervation pattern in the rat portal vein has been studied with the histochemical fluorescence method of Hillarp and Falck. Stretch preparations and transverse freeze-dried sections of intact portal veins were studied from rats during the first 5 weeks of life and from adult rats. Orientation of undifferentiated smooth muscle cells into two layers was observed at 4 days of age. Dominance of the thick outer longitudinal muscle layer was apparent at two weeks of age. A terminal adrenergic nerve plexus with some varicosities was restricted outside the media at the end of the first week. Ingrowth of penetrating non-terminal adrenergic nerve fibers through the longitudinal muscle layer occurred during the second week of age when the main terminal nerve plexus was developing between the two muscle layers. After 3 weeks of age the adult pattern of a two-dimensional adrenergic plexus between the muscle was established. In the adult rat pharmacological treatment with nialamide and noradrenaline revealed the thin, penetrating non-terminal adrenergic nerve fibers in the longitudinal muscle layer which were poorly visible otherwise. The present observations strongly indicate that the main adrenergic plexus between the two muscle layers emanates directly from the outer axonal plexus. These findings are discussed regarding possible trophic interactions between ingrowing sympathetic adrenergic vasomotor nerves and maturing vascular smooth muscle.


Ultrastructural details of Sertoli cell junctional complexes in vivo and their modifications in tissue culture. This study was carried out using thin sections, lanthanum tracing, and freeze-cleaving in order to investigate the Sertoli cell junctions of rat testis in vivo and their maintenance in culture. The presence of a new type of membrane specialization has been revealed. This consists of a close association between tight junctions and nexuses. The Sertoli cell contact specializations show a progressive disorganization in vitro correlated with the duration of the period in culture. The relationship between the morphological changes in Sertoli cell junctions and the lack of spermatogenesis in culture is discussed.


Granulolysis in neurosecretory neurons of the rat supraoptico-posthypophyseal system. Ultrastructural and cytochemical observations on neurosecretory neurons of the rat supraoptico-posthypophyseal systems were made under experimental conditions which resulted in striking changes in the amount of neurosecretory granules and lysosomes. Attention was focused on granulolysis. At the onset of rehydration following a 4 days water deprivation, very active autophage took place in neurosecretory axons of the neural lobe involving the marked increase in smooth endoplasmic reticulum, microvesicles and neurosecretory granules, although the latter were still very few due to previous depletion. When axonal transport was inhibited by colchicine at the onset of rehydration, granules accumulated in the perikarya while granule reloading of the neural lobe was delayed. However autophagy, although always active in axons, remained scarce in perikarya. Moreover, in the latter there was only slight evidence of crinophagy. Hypophysectomy also induced granule accumulation in the perikarya, although accompanied by little granulolysis. Images indicative of crinophagy as shown by acid phosphatase localization were few and exclusively restricted to perikarya, while autophagy occurred essentially in axons. Autophagy appeared to be the predominant process for granulolysis and might be considered here as an aspect of the general turnover of cell constituents, related to the sudden regression of hyperactivity-induced hyperthrophy, rather than as an expression of a specific regulation of an excess of secretory material.


Heterotopic allotransplantation of isolated aortic cells. An electron microscopic study. Smooth muscle cells were enzymatically isolated from the tunica media of the aorta of 5-day-old rats. Following in vitro exposure to colloidal thorium dioxide particles the cells displayed numerous lysosomes filled with these particles. Intramuscular injection of isolated cells into the tongues of young rats of the same strain, resulted in the formation by both freshly isolated and thorium dioxide-labeled cells of a characteristic tissue similar to that found in the intact aortic wall. Thus, the transplants consisted of typical smooth muscle cells surrounded by an extracellular matrix consisting of a microfibrillar network, patches and fibers of elastin, collagen fibrils and small polygonal granules believed to represent proteoglycans. This system can be used for experimental studies on the production of extracellular matrix components and on other functions of arterial smooth muscle cells growing outside the vascular wall.


Adrenal glomerulosa mitotic stimulation by posterior pituitary hormones. Injection of posterior pituitary powder induces an intense mitotic stimulation in the zona glomerulosa of the adrenal gland of young rats. This effect is much more pronounced in females than in males. It is maximal at two days treatment. Longer periods result in a hypertrophied zona glomerulosa and lower mitotic activity. A search for the hormone responsible for the stimulation shows that vasopressin, and to a lesser extent oxytocin, are mitogenic. ACTH, alpha-MSH, beta-MSH and the pineal hormones have no effect. Renin (but not angiotensin) induces a significant stimulation. It is concluded that vasopressin exerts a potent influence on the glomerulosa. This is in contrast with the prevalent view that the glomerulosa is little affected by the hypophysis.


Ultrastructure of the organum vasculosum of the lamina terminalis of the Japanese quail, Coturnix coturnix japonica. The structure of the organum vasculosum of the lamina terminalis (OVLT) of the Japanese quail has been studied by light and electron microscopy. The OVLT has a palisade arrangement. It forms a part of the terminal plate extending from the optic chiasma to the anterior commissure and is characterized by a special vascular arrangement. The organ consists of ependymal, internal and external zones. The ventricular surface of the organ is covered by non-ciliated ependymal cells characterized by the presence of raspberry-like ventricular protrusions. The ependymal zone is composed of two types of ependymal cells, one being a large, cuboidal cell with columinous cytoplasmic protrusions suggesting secretion into ventricle, and the other a slender tanycyte with long balar plexus of the external surface. The internal zone contains two types of secretory neurons, parvocellular neurons containing a few dense-cored granules 1,000 A in diameter, and mediocellular neurons containing in their perikarya many larger granules 1,300-1,500 A in diameter and well developed granular endoplasmic reticulum and Golgi apparatus. The granular formations are usually observed in the Golgi area of both types of cells, thus indicating of their secretory activities. There are three types of nerve terminals in the neuropil: (1) nerve endings containing spherical, dense-cored granules 800 A in diameter, which display axosomatic synapses with perikarya of the neurons, (2) nerve endings containing dense-cored granules 1,000 A in diameter and clear vesicles 400 A in diameter, and (3) nerve endings containing dense granules 1,300 A in diameter and clear vesicles. Types 2 and 3 do not display axo-xomatic synapses but often show axo-dendritic synaptic contacts with dendrites in the neuropil; thus they are probably axons originating from the parvocellular and mediocellular neurons of this organ. The functional significance of the neurons and axons of the OVLT is discussed and it is suggested that two kinds of neurohormones may be secreted from the OVLT of the Japanese quail.


Investigations on the turnover of adrenocortical mitochondria. V. An autoradiographic study of the radioactivity decay in the mitochondrial compartment from the adrenal cortex of 3H-thymidine-injected rats. The radioactivity decay of the mitochondrial compartment of 3H-thymidine-injected rats was followed by high resolution autoradiography. The number of days in which the radioactivity of the mitochondrial compartment is reduced to a half was calculated from the semilogarithmic plots of radioactivity versus time. Since DNA is a very stable molecule, it was assumed that this parameter can be an estimate of the half-life of adrenocortical mitochondria. It was found that the half-lives of mitochondria from the zonae glomerulosa, fasciculata and reticularis are, respectively, 8.20, 11.51 and 8.16 days.


Ultrastructure of perfusion-fixed fetal capillaries in the human placenta. The ultrastructure of human placental capillaries was investigated using perfusion fixation and the freeze-fracturing technique. The capillaries have a continuous endothelium especially rich in microfilaments, whereas micropinocytotic vesicles are exceedingly scarce. The endothelial cells are connected by three types of junctions: (1) zonulae occludentes characterized by 2 to 4 focal regions of membrane contact in thin-sectioned specimens and an equal number of ridges on the membrane E-face in freeze-fractured specimens; (2) small gap junctions associated with the zonula occludens. (3) attachment plaques resembling zonulae adhaerentes in their fine structure. Endothelial cells are provided with long, circularly oriented pseudopodial extensions, which may be responsible for intermittent constrictions of the vessel lumen. These findings indicate that diaplacental transport at the level of the fetal capillary is controlled by the cytoplasm of the endothelial cells and probably occurs only to a very limited extent by way of micropinocytotic vesicles.


Tritiated thymidine autoradiographic study on cellular migration in the gastric gland of the golden hamster. Ten hamsters received repeated injections of 3H-thymidine for 4 days and were allowed to survive for 7, 28, 42 and 100 days. Changes in spatial distribution of the labelled cells and in labelling indices of each cell line in the gastric glands were studied at various days after 3H-thymidine, the labelled parietal cells and the mucous neck cells were concentrated at the neck area. Starting from the neck area, they migrated an average of 3 micra downwards per day. By 42 days, they reached the middle level of the glands, where the labelled mucous neck cells decreased but the labelled chief cells increased in number. The differentiation of the chief cell then appears to take place at the middle level of the glands through transformation of the migratory mucous neck cells. After 4 days of the labelling, about 1.8% of the chief cells located in the lower part of the glands was found to undergo in situ replication. This indicates that the renewal of this cell type is partly assured by its own mitotic activity. The foveolar cell--the future surface epithelium--seems to migrate upwards along the long axis of the glandular tubule in the pipe line system, which means "first produced, first migrates". After migrating out from the neck area, the parietal cell and the mucous neck cell (the future chief cell) take an average of 200 days to reach the lower end of the glands. In the process of migration, however, the cells produced contemporaneously at the neck area became scatteringly spread from the neck towards the bottom of the gland. The time required for the newly-formed cells to reach the lower end of the gland varied between 100 and 300 days. In the gastric glands the cells first produced at the neck area do not first reach the lower end of the glands. This mode of random migration is referred to as the "stochastic flow system". As one of the probable factors which disturb the pipe line flow of downward cell migration, cellular movements perpendicular to the long axis of the glandular tubule were suggested to occur at random at any level of the gastric glands.


The marginal sinus in the perifollicular region of the rat spleen. The marginal sinus in the spleen of the Wistar rat surrounds the follicle and has more numerous PAS positive fibers on the inner wall than on the outer wall. India ink- and lead oxide-gelatin were injected into the abdominal aorta. It was found that much of the india ink-gelatin accumulated in the marginal sinus, the marginal zone, and part of the red pulp, while most of the lead oxide-gelatin collected in the marginal sinus. Ultrastructurally, the capillaries of the follicle were found to open into the marginal sinus. Regions not perforated by the marginal sinus lie between the follicle and the marginal zone. The wall of the marginal sinus is discontinuous and the discontinuities are wider on the marginal zone side than on the follicle side. The relationship of these findings is discussed.


A comparative study of the pineal complex in the deep-sea fishes Bathylagus Wesethi and Nezumia liolepis. The pineal complexes of two deep-sea fishes, Bathylagus wesethi (family Bathylagidae) and Nezumia liolepis (family Macrouridae), were studied with both light and electron microscopy. Receptor and supportive cells were identified in the pineals of both species. The presence of receptor cells suggests that the pineals function in photoreception. Ganglion cells could be identified only in B. wesethi. A dorsal sac and a paraphysis were found in B. wesethi; both structures are absent in N. liolepis. Several trends were found when the results of this study were compared with those of a study on the pineal complex of another deep-sea fish, the myctophid Triphoturus mexicanus (McNulty and Nafpaktitis, 1976). Two of these trends, which are correlated with the vertical distributions of the species studied, suggest an increase in the photosensitivity of the pineals. These are: 1) an increase in the average number of outer segment lamellar membranes per receptor cell, and 2) an increase in the ratio of receptor cells to nerve fibers in the pineal stalks. A functional relationship between the dorsal sac, paraphysis, and pineal central lumen was suggested. The relationship may involve secretory activities.


Origin, concentration and structural features of human mammary gland cells cultured from breast secretions. This study traced the origin of cells observed in human breast secretion samples obtained during lactation and describes the appearance of these cells following prolonged maintenance in vitro. Human milk contains a large number of single vacuolated foam celsl and a small proportion of non-vacuolated epithelial cells in clusters. Foam cells are identified by their large size, the polarity of their cytoplasmic organelles, the variation in number and size of lipid vacuoles and the condensed chromatin of their eccentrically located nucleus. Both cell types originate by exfoliation from the mammary gland. This was established by comparing the structural characteristics of cells isolated from milk with those of the cuboidal cell linings of ducts and alveoli in lactating mammary tissue. Relatively pure populations of foam cells could be established from early lactation samples (3-7 days post/partum) while non-vacuolated epithelial cell clusters were more frequently cultured from late lactation specimens (1-10 days postweaning). Foam cells did not divide and lost cytoplasmic organization during prolonged culture. In contrast, non-vacuolated epithelium in clusters proliferated to form colonies of polygonal cells. These results, which imply that foam cells are an active form of the non-vacuolated mammary cells in clusters, call attention to one system for the study of the complex hormonal interactions necessary to induce and maintain lactation.


Mitochondrial abnormalities in human phaeochromocytoma. Mitochondrial abnormalities are reported in four cases of phaeochromocytoma. These abnormalities include swelling and scant cristae, intramitochondrial dense bodies, septate-like junctions, intercristal fusion plus spheroidal bodies, and intramitochondrial rodlets. These structural mitochondrial changes are associated with reduction in activity of the mitochondrial enzymes, monoamine oxidase and succinic dehydrogenase.


Substrate dependence of cell migration from explanted neural tubes in vitro. Embryonic chick neural tubes containing neural crest cells were cultured in vitro on tissue culture plastic and collagen. Two parameters, the time of onset of cell migration from the neural tube and the rate of movement of the cell front away from the neural tube explant, were determined. On collagen, cell migration consistently began after four to six h in vitro, about five h prior to the onset of cell migration on tissue culture plastic. The identity of the migrating cells as neural crest cells is established by their eventual differentiation into melanocytes. Ablation experiments reveal that collagen also causes the early onset of migration of cells not of neural crest origin. These results provide in vitro support for the idea that extracellular materials may alter cell migratory behaviour in morphogenesis.


Small granulated cell types in rat superior cervical and coeliac-mesenteric ganglia. In the rat superior cervical and coeliac-mesenteric ganglia we have observed three types of small granulated (SG) cell: Type I cells are characterised by membrane-bounded cytoplasmic granules with a core of variable, moderate to low electron-density, whose limiting membranes are rounded in profile ranging from 50-150 nm in diameter. Type II SG cells contain numerous highly electron-dense, polymorphic cytoplasmic granules ranging from 100-300 nm in diameter. The haloes of Type II cell granules are variable in shape, and the core is often eccentrically located or fragmented. Type III SG cells contain membrane-bounded granules with a core of variable moderate to low electron-density. In profile these granules appear oblong or circular with average dimensions of 170 x 50 nm. All three SG cell types receive cholinergic-type pre-ganglionic terminals whose afferent nature is confirmed by their degeneration following pre-ganglionic neurectomy. Only Type I cells have been observed to donate efferent synapses to dendrites of principal ganglionic neurones and are thus interneuronal.


The structure and innervation of the sinu-atrial node of the mole heart. The sinu-atrial node in the heart of the mole, Mogera wogera, contains myocytes which are devoid of atrial specific granules and which may be classified into two types: electron-lucent (majority) and dark (minority). Numerous unmyelinated axon terminals, containing synaptic vesicles, face the nodal myocyte surface with interspaces of less than 300 nm. There are about 6 terminals per myocyte profile and about 10 per profile at nuclear levels. Of a total of 2717 of these terminals 85.2% are 50-200 nm from the nodal myocytes, and 9.6% form closer neuromuscular junctions, with less than 50 nm interspace and some membrane specialization. Such specilizations are almost exclusively found in relation to the dark, minority-type of nodal myocyte. Myelinated nerve fibers are also numerous within the mole SA node, and may terminate almost directly on a nodal myocyte. A few nerve fibers contain many mitochondria and may represent afferent endings. Nodal capillaries are smaller and fewer than capillaries in the juxtanodal myocardium, probably indicating a lesser blood supply to the SA node than to the ordinary myocardium.


Electron microscopy of the rabbit pineal organ in vitro. Evidence of norepinephrine-stimulated secretory activity of the Golgi apparatus. The results presented in this study show that the rabbit pineal organ cultured in vitro retained its in vivo fine structure for at least eight days. However, the Golgi complex in the light pinealocytes stopped forming dense core vesicles while vesicle-crowned ribbons increased in number. After addition of norepinephrine to the culture medium, the Golgi complex once more began the production of dense core vessicles. Terminals of light pinealocytic processes then often contained Golgi dense core vesicles in close contact with the cell membrane, suggesting the release of the vesicular content into the intercellular and perivascular spaces. A close topographical relationship between Golgi dense core vesicles and vesicle-crowned ribbons was observed.


The aesthetes of chitons. III. Shell surface observations. The shells of the chitons Lepidochitona cinereus, Sypharochiton pelliserpentis, Amaurochiton glaucus and Onithochiton neglectus were examined by scanning electron microscopy. In all species the surface terminations of the megalaesthete and micraesthete organs could be identified lying flush with the shell surface, as well as, lenses of the shell eyes in O. neglectus. Periostracal debris and encrusting diatoms were a usual feature of the shell surfaces. The micraesthete subsidiary caps normally appear featureless, but the megalaesthete apical caps sometimes appear to be perforated. The reasons for this perforate appearance are discussed and it is concluded that it provides no evidence for the normal passage of substances out of or into the megalaesthete.


Studies on the fine structure of invertebrate blood vessels. II. The valves of the lateral sinus of the leech, Hirudo medicinalis L. The position, structure and function of the valves within the lateral sinus of the medical leech, Hirudo medicinalis, are described on the basis of vital, light- and electron microscopy. In this species the valvular apparatus consists of multiple elongated fir cone-shaped fibrous villi surrounding the orifices of the latero-lateral and latero-dorsal vessel like a tentacular crest. Each villus is covered by a thin sheet of a continuous endothelium. The valves prevent the backflow of hemolymph during systolic contraction of the lateral sinus. The endothelium contains many small mitochondria and polyribosomes in the perinuclear cytoplasm and it develops deep projections into the underlying connective tissue. Each of these consists of a multilayered system of closely interwoven thin endothelial membranes. The endothelium is anchored to its basement membrane by means of a great number of poorly defined hemidesmosomes. The fibrous tissue of the villi consists mainly of a homogeneous vitreous matrix in which few cellular components and very fine filaments are dispersed. Close to the endothelium this matrix appears to be condensed to form a multilayered framework made out of a basement membrane-like material. Though the valves themselves are devoid of muscle cells, those situated at their base and thus belonging to the vascular wall proper, display some specific morphological features: in particular the nuclei of these cells show a distinct fibrous lamina. Moreover, these muscle cells seem to be innervated only by one type of axon, containing both small, lucent synaptic vesicles  as well as some of the dense-core variety. These findings are compared with data from earlier works and are discussed in relation to the hemodynamic functions of this valvular apparatus.


Degeneration of monoamine nerves in anterior byssus retractor muscle of Mytilus induced by 5,6-dihydroxytryptamine. Preliminary ultrastructural studies on the effects of 5,6-Dihydroxytryptamine (5,6-DHT) on the anterior byssus retractor muscle (ABRM) of Mytilus show degeneration of 2 types of monoaminergic nerves after 10 days of drug treatment. One type contained large granular vesicles (560-1,680 A) possibly represent serotonergic and dopaminergic nerves, thought to innervate this muscle. Two other types of profiles seemed to be unaffected by the drug. One conforms to cholinergic nerves while the other has a predominance of large opaque vesicles (1,200-2,500 A). The significance of these findings is discussed in the light of recent observations on the neurotoxic effects of 5,6-DHT on vertebrate and molluscan nerves.


Cell junctions in the epithelium of Bowman's capsule. The intercellular connections between the epithelial cells of Bowman's capsule were investigated. It could be demonstrated that typical zonulae occludentes (tight junctions) are present in the species (rat, hamster, and Tupaia) studied. Freeze-fracturing shows a network of anastomizing strands; some species variations are described. In the rat two strands are common. In the golden hamster mostly two to four and occasionally five strands occur. In Tupaia regularly three tight junction strands are found and also gap junctions associated with the zonulae occludentes. In thin sections the goniometric analysis confirms the freeze-fracturing results and reveals attachment zones of macular shape, which are classified as intermediate junctions and desmosomes. The functional role of these cell junctions observed in the epithelium of Bowman's capsule is discussed.


Ultrastructural study of the shell-repair membrane in the snail, Helix pomatia L.. The shell-repair membrane of the snail, Helix pomatia, has been studied with the transmission electron microscope (TEM). The ultrastructure of the repair membrane, in the initial stages of calcification, revealed the presence of a fibrillar protein, proteoglycan granules, osmiophilic vesicles, and cytoplasmic dense bodies of different size and structure. The involvement of the cell constituents in the formation of calcifying centra and initial crystal formation is discussed. The amoebocytes present within the repair membrane appeared to be involved in three different functions: (1) phagocytosis, (2) release of granules, vesicles and dense bodies, and (3) secretin of a fibrillar protein. The possible lytic function of the amoebocytes is mentioned. The common features in the minearlizing process of the shell-repair membrane of the snail and the epiphyseal cartilage of the mammals were noted.


Fine structural observations of sperm resorption in the seminal vesicle of a marine snail, Littorina scutulata (Gould, 1849). Waste sperm and spermatozeugmata in the seminal vesicles of Littorina scutulata are phagocytised either by cell buds (large vesicles given off from the epithelial cells) or by the epithelial cells themselves. Cell buds containing sperm, are in turn engulfed by epithelial cells. In both cases, heterophagic vacuoles are formed inside of the cell and subsequently the vacuoles are fused with primary lysosomes or lysosomal derivatives to become secondary lysosomes. Throughout this process the sperm are being digested. The second lysosome transforms further to telolysosome and finally to residual body when the sperm is completely digested.


Localization of monoamines in the corpora cardiaca and the hypocerebral ganglion of locusts. The Falck-Hillarp method reveals yellow and green fluorescent areas in the neurohemal part of the corpora cardiaca. Some neurons and the neuropile of the hypocerebral ganglion appear green. The localization of triatiated serotonin taken up and stored in the corpora cardiaca was studied radioautographically in vivo and in vitro with the use of low concentrations of tritiated serotonin. In the neural part of the corpora cardiaca, fibers with 100 nm dense granules were shown to be indolaminergic. Fibers containing 200 nm dense granules and 250 nm clear vesicles are thought to be catecholaminergic.


Hatching glands in salmonid fishes, Salmo gairdneri, Salmo trutta, Salvelinus fontinalis and Salvelinus pluvius. The unicellular hatching glands (UHGs) of four species of salmonid fish, Salmo gairdneri, Salmo trutta, Salvelinus fontinalis and Salvelinus pluvius were studied by light and electron microscopy. The UHGs are distributed on the epidermis of head and yolk sac, and on the epithelium of the mouth and gills. Since these cells are large and include dilated cisternae of the endoplasmic reticulum from the primitive to the mature stages they are conspicuous. Around the Golgi complexes, there are consecutive figures showing synthesis of secretory granules with close relationships to the Golgi vesicles. The secretory granules grow in size and vary in density during maturation; some have enclosed cytoplasmic structures. At the hatching stage, they are discharged with some cytoplasmic structures from the UHG which is located in the superficial layer of epithelium. After exhaustion of the secretory granules, the remainder of the contents of UHGs is liberated.


Intestinal endocrine cells of chicks around the time of hatching. The duodenum of 16-day Black Australorp chick embryos, and the duodenum, ileum, large intestine and caeca of 18-day embryos and of chicks within 30 h of hatching, have been studied by electron microscopy. Cells were found with secretory granules resembling those in mammalian EC, S, A-like, EG and D cells (terminology of Solcia et al., 1973), and were on this basis tentatively identified accordingly. The distribution and frequency of the chick cells in different parts of the tract correspond well to the situation in mammals.


Endocrine cells of the stomach of chicks around the time of hatching. The proventriculus, gizzard and pyloric antrum (region between the gizzard and the duodenum) of 18-day Black Australorp chick embryos and of chicks within 30 h of hatching have been studied by electron microscopy. D and EC cells, and putative G, D1 and A-like cells were identified (terminology of Solcia et al., 1973) but no ECL cells. No endocrine cells of any kind were revealed in the gizzard.


Innervation of the carotid body of the adult rat. A serial ultrathin section analysis. The innervation of the carotid body of adult rats was studied by means of serial ultrathin sections. A single branching nerve fiber innervates 12 chief cells through several kinds of terminals (vesicle-containing, mitochondrial sack, and calyx-type) in en-passant and bouton forms.Two types of synaptic contacts between nerve terminals and chief cells are found; type 1 in which chief cells are postsynaptic, and type 2 in which chief cells are presynaptic. Since a single nerve fiber (possibly from the glossopharyngeal nerve) forms both types of synapses with type 2 predominating, the nerve fiber is considered basically sensory or centripetal. In addition to their synaptic connections with sensory nerve fibers, chief cells located in the periphery of this organ are in synaptic relation with dendrites of a few ganglion cells adjacent to these cells. Here the chief cells are presynaptic. A few synaptic contacts between two adjacent chief cells are seen, and so are direct contacts between thief cells and preganglionic efferent nerve fibers terminating on ganglion cells.


Mesothelial intercellular junctions and pathways. Freeze-etch preparations of mesothelial cells taken from the peritoneum of mouse reveal the presence of vesicles invaginating the apical and the basal cell surfaces. These vesicles are scarcely seen within the cytoplasm. Long tortuous tubular profiles extend for considerable distance within the cytoplasm and are frequently associated with the vesicles. The possible nature and role of the vesicles and the tubules in transport phenomena across the mesothelial barrier, are discussed in relation to the pore theory advanced by physiologists and the "stomata" concept observed by early German and contemporary anatomists. "Occludens" junctions of the leaky type are seen though their macular or zonular nature is yet to be established.


Formaldehyde induced catecholamine fluoroscence in the mouse inferior laryngeal paraganglion. The presence of high concentrations of catecholamines is shown in the mouse's inferior laryngeal paraganglion by means of fluorescence histochemistry. In mice, the entire organ is composed of 20 to 25 small, intensely fluorescent cells of oval shape (about 15 mum in diameter). The paraganglion is well provided with capillaries. The identification of catecholamines in the inferior laryngeal paraganglion, originally described as nonchromaffin (parasympathetic) paraganglion, presents additional evidence that all paraganglia store biogenic amines, are related to the sympathetic nervous system, and belong to the APUD cell series.


Electron microscopy of two types of reflecting chromatophores (iridophores and leucophores) in the guppy, Lebistes reticulatus Peters. Reflecting chromatophores in the integument of the guppy, Lebistes reticulatus Peters, are of two distinct types, iridophores and leucophores. The iridophores are smaller and fixed, producing a metallic iridescent color. The cytoplasmic organelles involved in the coloration of iridophores are the reflecting platelets, as in the iridophores of other fish and amphibian species on which earlier reports have been made. Spherical granules of pleiomorphic internal structure, quite variable in size but generally 0.2 mum to 1.0 mum in diameter, are also numerous in the iridophores. The nature of these granules remains unknown. The leucophores are larger, and highly dendritic; their pigment granules are migratory and they exhibit a dull whitish color. Pigment granules of the leucophores are spherical in form, varying from 0.5-0.8 mum in diameter, with a double membrane enclosing the internal fibrous materials. Melamine-treatment of the fish caused degenerative changes in the pigment granules and also the other cytoplasmic organelles of the leucophores, whereas the other kinds of chromatophores, including the iridiophores, remained intact. Some problems in general characterization and classification between these two types of chromatophores were discussed.


Effect of a low calcium diet on the ultrastructure of the parathyroid gland of chicks. The effect of a low calcium diet on the ultrastructure of the parathyroid gland in the chick was examined. Two-week-old White Leghorn chicks were fed a low calcium diet (calcium content 0.63%) for two weeks. In these chicks, the parathyroid glands are grossly enlarged. Hypertrophy and hyperplasia of the chief cells are evident. The plasma membranes between adjacent cells are relatively straight but interdigitate in some places. Chief cells contain occasional membrane-limited secretory granules (150-350 mmu in diameter) and with contents of variable electron density. Secretory granules are distributed randomly but some are closely applied to the plasma membrane. There is an increase in the development of the rough-surfaced endoplasmic reticulum. The Golgi complex is enlarged and consists of cisternae arranged in concentric layers, smooth-surfaced and coated vesicles and condensing vacuoles. Dilatations of the cisternae at several points are observed. Mitochondria and filaments are also encountered. These morphological features suggest that low calcium intake stimulates the synthetic activity of the chief cells of the chick parathyroid.


Electron microscopic studies of the pressoreceptor fields of the carotid sinus of the dog. In the dog, pressosensitive endings of the sinus nerve extend along the border between the adventitia and media of the carotid sinus wall. The axon endings, containing a great number of mitochondria, can be divided into small (600-2,000 nm) and large (6,000-8,000 nm) end swellings. In the terminal region the pressosensitive fibers are surrounded by ramified and highly structured Schwann "terminal cells". The topographic location in relation to elastic and collagenous tissue indicates a functional connection between receptors and efferent nerve endings in the immediate surroundings has been discussed in this report. Several axon endings contain variable amounts of glycogen which is regarded as an indication for the inactive metabolic state of the ending. Axonal swellings demonstrate considerable modification in structure, such as loss of structural integrity in mitochondria, the formation of lamellar fields, vesicular irregularities and disintegration of axoplasm, all of which are considered as the morphological expression of "wearing out", degeneration and possibly regeneration.


Ultrastructure of the ampullary electroreceptors in lungfish and Brachiopterygii. Electron microscopy shows that the electroreceptors of Protopterus dolloi (Dipnoi) and Calamoichthys calabaricus (Brachiopterygii) are very similar to the known ampullary electroreceptors of other primitive fish groups. With Protopterus, however, there is one difference: at the apical surface of the receptor cells, instead of a kinocilium, a club-shaped protrusion is found. The club-shaped protrusion has no fixed number nor a fixed arrangement of microtubules (Fig. 4). The presynaptic ribbons are in direct contact with the presynaptic membrane, and may be invaginations of the presynaptic membrane (Fig. 3). The functional significance of the kinocilium and of the club-shaped protrusion is discussed. Furthermore, a possible biological role of the ampullary electroreceptors in fish coming into frequent contact with the water surface (Dipnoi, Brachiopterygii) is considered.


Morphology and ultrastructure of the antennal chemoreceptors and mechanoreceptors of worker Coptotermes formosanus Shiraki. Three types of setae were found on the antenna of workers of C. formosanus. Sensilla basiconica function as chemoreceptors. They are non-socketed, with fixed plate base, thin walled, and perforated. Pore tubules are contained within the cuticular pores of s. basiconica. The pore tubules have direct contact with the dendritic branches within the sensilla. The other sensilla are tactile mechanoreceptors. The longest setae (sensilla trichodea) are thick walled, socketed, mononeuronic, and non-perforated. The shorter mechanoreceptors (sensilla chaetica) have the same characteristics as s. trichodea, except that they are sometimes dineuronic. The numbers and distribution of the sensilla were established.


The elastic cartilage in the normal rat epiglottis. I. Fine structure. Chondrocytes of the rat epiglottis contain large amounts of glycogen and lipids, which often make the cells resemble fat cells. The content of lipids is interpreted as being related to the function of the cells. The membranes of some of the large vacuoles are stained with ruthenium red. The cells give rise to long cytoplasmic processes. As in hyaline cartilage the intercellular substance consists of a fine network containing proteoglycan granules together with thicker cross striated fibers. Furthermore elastic fibers are found, consisting of amorphous and microfibrillar parts. In the matrix, both lysosome-like granules and more or less empty vesicles are observed. Accumulations of a finely particulate electron dense material and of a translucent amorphous material containing membrane bound granules are found in some lacunae situated in the outer part of the cartilage. These accumulations are possibly related to the development of collagenous and elastic fibers.


Effects of light and dark upon photoreceptor synapses in the retina of Xenopus laevis. Photoreceptor synapses in Xenopus retina were studied after exposure to day/night cycles and continuous light or dark. In the rods, dense-core vesicles appear alongside the synaptic ribbons in animals exposed to light. In dark-adapted rods, electron-dense material is present in the synaptic clefts, but no dense-core vesicles are found associated with the synaptic ribbons. Cone photoreceptors do not show these ultrastructural changes in response to light and dark. Prolonged exposure to light (21 days) causes flattening of the synaptic vesicles associated with the synaptic ribbons in both rods and cones. The results are discussed in the light of what is known about transmitter release from photoreceptors.


The sympathetic innervation of the ciliary body and trabecular meshwork of the cat. Fluorescence histochemistry and electron microscopy. The ciliary body of the cat was investigated by fluorescence histochemistry and electron microscopy in an attempt to clarify its sympathetic innervation. Subconjunctival doses of 5-hydroxydopamine (5-OHDA) or 6-hydroxydopamine (6-OHDA) were given to establish the precise location of the sympathetic nerve terminals. The distribution of noradrenergic fibers and terminals was shown by fluorescence histochemistry to be sparse in the trabecular meshwork and the anterior portion of the ciliary muscle, but dense in the subepithelial tissue. The small and large dense core vesicles which occur in many nerve endings of the subepithelial tissue adjacent to the pigmented epithelial layer increased in electron density following the administration of 5-OHDA. Many degenerating nerve endings were found in the same region of animals treated with 6-OHDA. In contrast, there were few noradrenergic terminals in the ciliary muscle except for a portion of the smooth muscle which was shown to be dually innervated. The noradrenergic fibers in the subepithelial region and the trabecular meshwork may play an important role in aqueous secretion and outflow.