Identification of a tumor-associated antigen in cervical carcinoma by two dimensional (crossed) immunoelectrophoresis.

Two-dimensional immunoelectrophoresis was used to evaluate 8 cervical cancer speciments, 11 other gynecologic tumors, and 5 specimens of normal cervix. Antigens were water-soluble tissue extracts and antisera prepared in rabbits. When tested against antisera to cervical cancer, cancer antigens showed 14-17 precipitin lines whereas normal cervix showed 10-16. A single heavy heterogeneous precipitin line with an electrophoretic mobility of 0.58 relative to bovine albumin was observed in all cervical cancer specimens but not in normal cervical or other tumor specimens. Further evidence for the uniqueness of this antigen was sought by enhancement (addition of another antigen to the first phase of electrophoresis which increased the size of common peaks) and suppression (addition of another antiserum to the second phase, whereby the peak size of components to which both sera have antibody was decreased). The specific precipitin line was neither suppressed by the addition of antisera to normal tissue nor enhanced when normal tissue antigen was added to the tumor antigen preparation. More conclusively, adsorption of the tumor antiserum with normal tissue had no effect on the unique tumor-associated precipitin line, whereas all other precipitin lines were removed. This antigen was common to other cervical tumors because enhancement was demonstrated with three other cervical tumor specimens. The identification of a distinct and separate antigen associated with cervical carcinoma will permit further characterization and possible development of immunodiagnostic methods.

Kinetics and dynamics of disopyramide and its dealkylated metabolite in healthy subjects.

The kinetics and dynamics of total and free (unbound) disopyramide (D) after dosing with D, 1.5 and 2 mg/kg iv, were compared with those of the dealkylated metabolite (MND) after dosing with MND, 0.5 and 1.5 mg/kg iv, in six healthy subjects. Dynamic parameters included ECG with measurement of the QT interval corrected for heart rate (QTc), systolic time intervals, vitamin C-stimulated saliva secretion, pupil size, and maximum accommodation capacity. Mean values of total clearance, apparent volume of distribution, and elimination t1/2 of MND were 5.9, 2.3, and 0.4 times those of total D, respectively. D significantly prolonged the QTc and systolic time intervals and induced transient inhibition of stimulated saliva secretion. In contrast, MND induced no substantial change in either the QTc or systolic time intervals, but did induce more persistent inhibition of salivary secretion. If anticholinergic potency is determined as the degree of inhibition of stimulated saliva flow per plasma concentration unit, MND was three times as potent as its parent when measured at maximum inhibition. There were no consistent drug effects on the ocular parameters. The effect of D on QTc correlated with both total and free plasma concentrations. Furthermore, its transient salivary inhibitory effect paralleled its initial rapid decline in plasma concentration. There was no relationship between the MND plasma concentration and its salivary inhibitory effect. We conclude that disopyramide significantly affected the QTc and systolic time intervals in healthy subjects, while MND in a similar dose had no such effects. MND more strongly inhibited stimulated saliva flow, indicating a more potent anticholinergic effect than D.

Detection of tumor-specific antigens in human mucinous cystadenocarcinoma of the ovary by immunodiffusion.

Rabbit antiserum to a tissue extract of human mucinous cystadenocarcinoma of the ovary reacted with tissue extracts of normal ovary and various ovarian malignancies, and ascitic or cystic fluids of ovarian origin by Ouchterlony double gel diffusion and precipitin inhibition techniques. The tumor-associated antigen(s) of mucinous cystadenocarcinoma, which were demonstrated by Ouchterlony double diffusion, were not present in tissue extract of pooled normal ovaries and cystic fluid of benigh tubo-ovarian cyst. An organ-associated tumor antigen as well as the type-specific tumor antigen may exist in mucinous cystadenocarcinoma of the ovary. The mucinous cystadenocarcinoma was not very immunologically different but was distinguishable from serous cystadenocarcinoma and other types of ovarian cancer by double gel diffusion. Precipitin-inhibition reactions demonstated that the adsorbed antiserum to human ovarian mucinous cystadenocarcinoma mixed with tissue extracts of dysgerminoma and serous cystadenocarcinoma, and ascitic fluid of papillary embryonal adenocarcinoma of the ovary could not eliminate the specific precipin line developed with tissue extract of mucinous cystadenocarcinoma.

Cytomegalovirus infection of the uterine cervix: local cervical infection and antibody response.

Thirty-three women were examined on three or more occasions, each at 2-month intervals. The overall recovery rate of cytomegalovirus (CMV) was 28% (60/215). CMV was recovered from 53% of the cases where the local antibody was 1 : 64 or greater but the greatest difference occurred below titers of 1 : 32. Below that level virus was recovered in less than 5%, compared to a prevalence of 35% for cases with a titer of 1 : 32 (P less than 0.001). Twenty-eight cases in whom CMV was sought underwent colposcopy examination and had cytologic smears examined by the papanicolaou method. The external uterine cervix with columnar cells only yield a CMV prevalence of 3/17 (18%). However, if colposcopy showed either atypical transformation or metaplasia the prevalence was 4/11 (36%). Similarly, it is provocative that the prevalence of CMV appears to increase with abnormal cytologic findings to 33% recovery in severe dysplasia or carcinoma in situ.

Distribution of moricizine in human blood: binding to plasma proteins and erythrocytes.

Using equilibrium dialysis and incubation experiments, we determined the binding of moricizine to human plasma, isolated plasma proteins, and erythrocytes. The mean (% +/- SD) plasma protein binding at various moricizine concentrations ranged from 81.2 +/- 2.1 to 89.9 +/- 2.1%. There was no apparent relationship between drug concentration and extent of binding in pooled plasma over the concentration range tested. However, protein concentration-dependent binding was observed with albumin and alpha 1-acid glycoprotein (alpha 1-AGP). The unbound fraction of moricizine fell from 61 to 19% and from 70 to 17% with increasing albumin (5 and 50 g/L, respectively) and alpha 1-AGP (0.2 and 1.2 g/L) concentrations. The binding of moricizine to beta-lipoprotein (5 g/L) was 70.6 +/- 3.1% and to gamma-globulin (12 g/L) was 13.6 +/- 3.3%. Moricizine partitioned into erythrocytes, showing an erythrocyte/plasma drug concentration ratio of 1.325 +/- 0.070 and erythrocyte/buffer ratio of 8.561 +/- 0.620. An estimation could be made that 57% of total drug in whole blood was associated with erythrocytes, 39% bound to plasma proteins, and 4% was free. The results of this study demonstrated that erythrocytes, albumin, and alpha 1-AGP were the major binding components in blood.

Circulatory and cellular immune responses to squamous cell carcinoma of the uterine cervix.

The sera from 176 patients with cervical cancer were examined by indirect immunofluorescence against cervical cancer cells (imprints of cervical cancer tissue). The mean serum titer in these patients was significantly higher than the titer in two control groups of identical size. These tumor-related antibodies were also higher in titer in sera from a small sample of nine husbands of cancer patients than in 18 control group patients. A cell-mediated immune response was studied with the use of leukocyte-migration inhibition from 39 blood specimens, including 23 patients with invasive epithelial carcinoma, five with intraepithelial carcinoma of the uterine cervix, six with other gynecologic diseases, and five without gynecologic disease. Migration inhibition was demonstrated for squamous cell carcinoma of the uterine cervix, suggesting a common specific cell-mediated response.

Cardiac arrhythmia and betel nut chewing--is there a causal effect?

Betel nuts are widely ingested in many countries, including Taiwan. They stimulate various autonomic and CNS reactions, but there have been no reports of cardiac toxicity. We treated 2 patients with cardiac dysrhythmias thought due to betel nut chewing. In case 1, a 44-y-old previously healthy male presented with chest tightness, dyspnea, diaphoresis and palpitation immediately after chewing 1 betel quid. He soon became breathless and died despite immediate cardiopulmonary resuscitation. In Case 2, a 28-y-old man suffered palpitations, epigastralgia, and chest distress following consumption of 4 betel quid. Paroxysmal supraventricular tachycardia was noted and terminated by repeated verapamil administration. The pharmacological properties of betel nuts and the time sequence of these cases raise the possibility of betel nut-induced cardiac dysrhythmias. The number of betel nut chewers in Taiwan continues to increase, suggesting there may be other cases of betel nut-related cardiac toxicities in the future.

Puerperal infectious morbidity: relationship to route of delivery and to antepartum Chlamydia trachomatis infection.

We investigated the relationship of route of delivery and of antepartum Chlamydia trachomatis cervical infection to selected forms of puerperal infectious morbidity, including intrapartum fever, or early (less than 48 hours) postpartum fever not attributable to infections of sites outside the uterus and late (48 hours to 6 weeks) postpartum endometritis. Infectious morbidity occurred in 27 (44%) of 62 women who underwent cesarean section and in 33 (10%) of 329 who underwent vaginal delivery (p less than 0.001). Postsection infectious morbidity was not correlated with C. trachomatis infection and was largely limited to early postpartum fever. Among women who underwent vaginal delivery, infectious morbidity occurred in 10 (34%) of 29 women with and in 23 (8%) of 300 without C. trachomatis infection (p less than 0.001), and chlamydial infection was associated only with intrapartum fever and late postpartum endometritis. Separate matched case-control analyses confirmed that cesarean section was associated with an increased risk of early postpartum fever (p = 4 x 10(-8)); whereas among women who underwent vaginal delivery, antepartum C trachomatis infection was associated with an increased risk of development of intrapartum fever or late postpartum endometritis (p = 0.002).

Erythromycin ointment for ocular prophylaxis of neonatal chlamydial infection.

We compared the efficacy of erythromycin ophthalmic ointment vs 1% silver nitrate drops for the prevention of neonatal conjunctivitis or respiratory tract infection from Chlamydia trachomatis. The organism was isolated from the cervix of 67 (12%) of 572 pregnant women. They gave birth to 559 infants who were randomly assigned to either prophylaxis immediately after birth. Thirty-six of 60 infants born to Chlamydia-positive women received silver nitrate; 24 received erythromycin. Twelve (33%) of the 36 infants who received silver nitrate had chlamydial conjunctivitis, but none of the 24 infants who received erythromycin did. Ten (29%) of 36 infants receiving silver nitrate had chlamydial nasopharyngeal infection (three later had pneumonia), as opposed to five (21%) of 24 who received erythromycin (one had pneumonia). Thus, erythromycin ointment is effective in prevention of chlamydial conjunctivitis, but it may not reduce nasopharyngeal infection or subsequent pneumonia.

Experimental nasopharyngitis and pneumonia caused by Chlamydia trachomatis in infant baboons: histopathologic comparison with a case in a human infant.

Three infant male baboons were inoculated with a strain of CHLAMYDIA TRACHOMATIS ISOLATED FROM A HUMAN INFANT WITH PNEUMONITIS. One baboon, inoculated by intratracheal, nasopharyngeal, and oropharyngeal seeding, had rales, radiographic evidence of pneumonia, persistent nasopharyngeal C. trachomatis infection, and a four-fold rise in titer of antibody. At sacrifice 24 days after inoculation, nasopharynx, trachea, airways, and lung yielded C. trachomatis, and epithelial inclusions were seen by light and immunofluorescent microscopy. Histopathologic changes noted were nearly identical to those in a lung biopsy specimen from a human infant and pneumonitis and nasopharyngeal C. trachomatis. The second baboon was inoculated by tracheal seeding and maintained nasopharyngeal C. trachomatis until killed 30 days later. Autopsy revealed nasopharyngitis and patchy mild pneumonitis. The third baboon was inoculated by nasopharyngeal seeding and maintained nasopharyngeal C. trachomatis for 49 days. Both of the latter baboons seroconverted. Infant baboons appear to be useful animal models for C. trachomatis nasopharyngitis and pneumonia.