[ELISA of human alpha-fetoprotein. A simple and highly sensitive method with the use of microplates].
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Biomedical subjects
Publications and source records attributed to Y Tsukada.
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Antibiotics having antitumor activity (anticancer drugs) also possess inevitable side effects on normal proliferating cells. In order to overcome these side effects, targeting chemotherapy has been developed using antibodies to specific tumor-associated antigens. In this experiment, polyclonal or monoclonal antibodies to AFP (aAFP) were selected for coupling to anticancer drugs such as daunomycin and adriamycin. Dextran (M.W. 10,000) was used as an intermediate drug carrier to increase the number of drug molecules bound indirectly to aAFP. This aAFP-dextran-anticancer drug conjugate produced a striking effect on AFP-producing tumor cells in vivo as well as in vitro using both rat AFP-producing hepatoma AH66 and human ovarian tumor growing in nude mice. The aAFP-dextran-adriamycin conjugate was administered to patients with hepatoma. Although the effect of the conjugate was unclear, long-term suppression of serum AFP level was observed in one case. No obvious side effect encountered.
Monoclonal antibody F36/22 recognizes high-molecular-weight glycoprotein components associated with neoplastic development of the ovary. Indirect immunoperoxidase staining techniques were performed on a panel of nonmalignant ovarian tissues, primary ovarian tumors, exfoliated ascitic tumor cells, and metastatic lesions. Normal ovarian tissue components (n = 20) failed to exhibit detectable levels of antigen, whereas benign ovarian tissues show a low incidence of immunostaining (three of 26) restricted to some ductal elements. One hundred % (19 of 19) of the immunopositive primary malignant tumors were histologically classified as adenocarcinomas. Each of the predominant adenocarcinoma histotypes consistently showed expression of the antigen with 30 to 100% of the tumor cells scored as immunopositive. Ascitic tumor cells obtained from all of the ovarian adenocarcinoma patients examined (47 of 47) displayed immunopositive reactions, whereas normal mesothelial cells in these specimens exhibited undetectable staining. In addition, ovarian adenocarcinoma metastases (12 of 12) exhibited very intense immunoreaction products. No detectable antigen was expressed by nonadenocarcinoma ovarian tumor cells.
Four Cynomologous monkeys (Mecaca fascicularis) received 2000 Rad whole brain irradiation. One remained untreated and exhibited loss of hair, facial edema, brain edema and hydrocephalus. There was loss of alertness and motor activity. One was scheduled to be treated with phenobarbital, but died in 24 hours after irradiation. One animal received 2 mg/kg dexamethasone I.M. daily. It died two weeks after irradiation apparently due to treatment related infection. One animal received 20 mg/kg sodium meclofenamate (Meclomen) orally daily. This animal showed no brain edema and only minimal hydrocephalus, delayed and incomplete hair loss and no facial edema. Further studies of this treatment appear to be justified.
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In recent years the colon urinary conduit has been used more frequently as an isolated urinary conduit at the time of total pelvic exenteration for recurrent carcinoma of the uterine cervix. This avoids an intestinal anastomosis and allows for the colon ureteral anastomosis to be outside of the previous irradiation field. Presented is the third case report of adenocarcinoma occurring in an isolated colonic urinary conduit, suggesting that careful surveillance for such malignancies may be required until the potential of neoplastic change is determined.
Ninety-four families totaling 201 cases are reported in this first report of the Familial Ovarian Cancer Registry. The results of the Registry and future studies are presented.
Central nervous system (CNS) metastasis was noted in 309 patients of 1044 autopsy cases of breast carcinoma. The brain was involved in 193 cases, and cranial dura in 167 cases. In 82 cases, the cranial dura was the sole site of CNS involvement. Metastasis to the leptomeninges was found in 59 cases, and to the spinal cord and dura in 32 cases. Metastases to the infratentorial portion of the brain was almost as frequent as to the cerebrum. Forty-two percent of the brain metastasis were single lesions, which is similar to the frequency of solitary metastasis to the brain from malignant tumors as a whole. CNS metastasis occurred more frequently in younger patients than older patients, and the clinical course of these patients was shorter than for those patients without CNS metastasis. CNS metastasis developed in the late stage of the disease, and often was not recognized clinically. Only 31% of the cases were clinically diagnosed or suspected before death. A median survival of these patients after clinical diagnosis of CNS metastasis was 33 days. However, a significant improvement was noted in the clinical diagnosis and median survival in the latter half of the study period. Eleven patients lived for more than 1 year after diagnosis of CNS metastasis. Only 14% of the 309 patients died from CNS failure.
Horse anti-alpha-fetoprotein was coupled to CM-cellulose discs by a modified carbodiimide reaction. The resulting coupling CM-discs were used in solid-phase radioimmunoassay of human alpha-fetoprotein. The sensitivity of these discs and conventional BrCN activated filter paper discs coupled anti-alpha-fetoprotein was approximately the same. A fair correlation between the alpha-fetoprotein levels determined by both methods was observed. The coupling procedure with carbodiimide is simple and the use of hazardous BrCN is eliminated.
Recently, the RTOG and ECOG concluded a joint randomized study on malignant gliomas that was in progress for the past five years. A total of 626 patients entered this protocol. Sixty-seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial. The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone. The four options were: (1) control radiation; 6000 rad/6-7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1-2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl-CCNU (125 mg/m2/day orally X 1 and repeat methyl-CCNU every 8 weeks), and DTIC (150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks). All pertinent patient characteristics were studied and several important prognostic factors have been identified. Notably, age, histologic type (Astrocytoma with anaplastic foci, versus glioblastoma multiforme), initial performance status, time since first symptoms and presence or absence of seizure. At this time, it appeared that there was no treatment option which was significantly better than the control. The study identified that age was the most important prognostic factor. Patients who were younger than age 40 years had an 18-month survival of 64%, patients who were age 40-60 years had an 18-month survival of 20%, and patients who were older than age 60 had an 18-month survival of 8%. The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40-60-year-old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups (P = 0.01, one-sided). Similarly, methyl-CCNU + DTIC was suggestively better than the control (P = 0.08, one-sided). The higher radiation dose, 7000 rad/8-9 weeks appeared to give no significantly better survival over the control dose option. Both BCNU and methyl-CCNU + DTIC produced some toxicity. The combination of methyl-CCNU + DTIC was more toxic than BCNU, producing severe or worse thrombocytopenia in 23% of the patients as compared to 6% on BCNU.
Reeler, a recessive mutation in mice, causes cytoarchitectonic abnormalities to the cerebral and cerebellar cortices. In normal controls, corticospinal (CS) tract neurons retrogradely labelled after HRP injection into the lumbar cord were situated only in layer V (the inner pyramidal layer). In the reeler, by contrast, the labelled CS neurons were scattered diffusely throughout all levels of the corresponding cortical area. In addition to the malpositioning of the somata, the labelled CS neurons in the cortex of the reeler could be divided into two major classes according to their dendritic pattern: typical pyramidal neurons and atypical ones. The typical pyramidal neuron had an apical dendrite projecting from the superior pole of the soma and ascending toward the pia mater and several basal and basolateral dendrites projecting from the inferior pole of the soma. The atypical neurons consisted of six types: (1) inverted, (2) tumbled, (3) bipolar, (4) V-shaped, (5) hook-shaped, and (6) superficial polymorphic. The typical pyramidal neurons in the reeler tended to be situated relatively deep in the cortex and the atypical neurons tended to lie relatively superficially in the cortex. The axons of both the typical pyramidal neurons and the atypical ones in the reeler usually extended from the lower surface of the soma or one of the descending dendrites as in the normal control.
This is a case report of a patient who had received radiation therapy for Hodgkin's disease and 48 years later developed adenosquamous carcinoma of the thyroid gland. Radiation associated thyroid carcinoma is usually of differentiated variety and carried no different prognosis than one not related to radiation. Coexisting adenocarcinoma and squamous cell carcinoma is a very rare event, but makes the prognosis of patients with thyroid carcinoma much poorer. As a result, this kind of patient requires early recognition and aggressive therapy.
Surgical specimens of malignant, supratentorial, astrocytic gliomas from 503 patients randomized on an RTOG-ECOG treatment protocol were examined by central pathologic review. The diagnosis of glioblastoma multiforme (GBM) was made only when one or more foci of coagulation necrosis involving astrocytic tumor cells were identified histologically. Malignant astrocytic neoplasms without necrosis were classified as astrocytoma with atypical or anaplastic features (AAF). The median survival stratifying for treatment for patients with GBM was eight months compared to 28 months for patients with AAF. In most cases the specimens were received with a Kernohan grade. On the basis of these grades, patients with astrocytoma Grade 3 had a median survival of ten months as compared to a median survival of nine months for those with astrocytoma Grade 4. Observations demonstrate that necrosis is a reliable, decisive prognostic factor associated with malignant, supratentorial, astrocytic gliomas. The Kernohan system is of limited value in assessing prognosis for this group of tumors.
Oligodendroglia in the "Shiverer" spinal cord at 2, 4, 8 and 18 weeks of age were investigated by electron microscopy, with special reference to the process of myelin formation. The predominant changes observed were vacuolization of the cytoplasm during 2 and especially 4 weeks of age, indicating initial steps in the formation of myelin sheaths, although their total volumes was very small and their lamellae were incomplete. Polymorphic vacuoles and vesicles with various electrondense contents appeared to originate from the Golgi complex and the rough-surfaced endoplasmic reticulum (r-ER), since such vacuoles happened to be continuous with the Golgi complex, and the Golgi complex disappeared concomitantly with the appearance of great numbers of vacuoles. The r-ER was also fragmented together with the occurrence of vesicles. After 8 weeks of age, the number of myelinated nerve fibers reached the plateau of the increasing curve, while the number of myelin lamellae successively increased until the sheaths were completed. At these stages the oligodendroglia containing vacuoles gradually disappeared, although numerous oligodendroglia possessing a nucleus with peripheral, densely clumped chromatin were present. These dark oligodendroglia contained a Golgi complex, r-ER with small, single cisternae and microtubules of irregular thickness, different from those found in the control oligodendroglia. At 18 weeks of age polymorphic vacuoles had disappeared in most oligodendroglia.
Using the indirect immunoperoxidase method, we studied the localization of carbonic anhydrase-III (CA-III) in frozen sections of biopsies of human skeletal muscle which had no definite pathology. CA-III was found to be localized in Type-I muscle fibers when compared with serial sections stained with myosin ATPase and other reactions. Our finding was in accordance with the biochemical data so far reported. It was though that CA-III could be used as a marker for abnormal Type-I muscle fibers in several neuromuscular diseases.
Injection of pregnant rats with cytosine arabinoside (ara-C) (280 mg/kg) on day 15 of gestation caused a significant rise (about two times the control value) in monoamine concentrations (norepinephrine, dopamine, and serotonin) accompanied by a decrease (about 60% of the control) in the brain weight and DNA content in the cerebrum of the offspring at 60 days of age. When neonatal rats were injected with ara-C (30 mg/kg/day) for four consecutive days from the fourth to seventh days after birth, a decrease of DNA content per cerebellum and an elevation of monoamine concentrations in the cerebellum were found. However, the total content of each monoamine per cerebrum or cerebellum showed no difference from the control. These results suggest that monoaminergic neurons may remain intact, with normal monoaminergic synapses compressed into a small brain volume. The neonatal administration of ara-C caused an elevation of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) (EC 3.1.4.37) activity and myelin protein content in the cerebellum, suggesting a relative increase in myelin concentration as a result of hypoplasia of granule cells.
This paper reviews the clinical characteristics of a group of patients in whom unsuspected primary adenocarcinoma of the colon presented with signs and symptoms of a primary ovarian neoplasia. In most patients, the ovaries were removed, the correct diagnosis was established at a later time, and a second surgery for resection of the primary adenocarcinoma of the colon was then performed. Preoperative use of colonoscopy or barium-enema examination would have helped. We compared these patients to a group of patients with similar clinical characteristics, but in whom the ovarian metastases were clinically apparent months after the resection of a primary colorectal cancer. We found that, in both groups, age of the patients, anatomic distribution of the primary tumor, histologic differentiation, serosal or mesenteric lymph node tumor involvement, and timing of the oophorectomy in relationship to removal of the primary colorectal tumor did not affect the overall survival. Once ovarian metastases were documented, patients died regardless of treatment, approximately 16 1/2 months after the diagnosis.
Treatment of agarose beads with mild acid (0.2 M HCl, 55 degrees C, several hours) hydrolyzes some of the glycosidic bonds between D-galactosyl residues and 3,6-anhydro-L-galactosyl residues, and thus produces aldehydo-groups useful for immobilization of amino compounds by reductive amination with NaCNBH3. More than 20 mg (0.3 mumol) of bovine serum albumin could be coupled per gram of partially hydrolyzed agarose beads. Arthrobacter neuraminidase immobilized by this method was useful for desialylation of sialyl glycoconjugates, and was found not to leach from the gel and to be much more thermostable than the free enzyme.