Ki-ras mutations are an early event and correlate with tumor stage in transplacentally-induced murine lung tumors

A previous study from this laboratory demonstrated that treatment of pregnant mice with 3-methylcholanthrene (MC) caused lung tumors in the offspring at 1 year after birth, the incidence of which correlated with fetal inducibility of Cyp1a1. Analysis by PCR amplification and allele- specific hybridization (ASO) of paraffin-embedded tumors generated from that study revealed the presence of point mutations in exon 1 of the Ki- ras gene. This work has now been expanded by PCR amplification and ASO analysis of 31 additional lesions. Point mutations were found in 37 of the 47 (79%) lesions analyzed in this and the previous study, the majority of which were G-->T transversions in the first or second base of codon 12. The mutational spectrum appeared to be dependent on the relative stage of differentiation of the lesion, as both the incidence of mutation and type of mutation produced correlated with malignant progression. Mutations occurred in 60% of the hyperplasias, 80% of the adenomas and 100% of the adenocarcinomas. In the lesions with mutations, GLY12-->CYS12 transversions occurred in 100% of the hyperplasias, 42% of the adenomas and 14% of the adenocarcinomas. The GLY12-->VAL12 transversions occurred in none of the hyperplasias, 42% of the adenomas and 57% of the adenocarcinomas. The remaining mutations, which consisted of ASP12 transitions and ARG13 transversions, occurred only in adenomas (17%) and adenocarcinomas (29%). Between this study and our previous analyses, the identity of the mutations obtained by ASO were confirmed by sequence analysis of eight of the 37 lesions that harbored mutations at the Ki-ras gene locus. There were no differences in the type or incidence of mutations relative to the metabolic phenotype or sex of the mice. These data suggest that mutational activation of the Ki-ras gene locus is an early event in transplacental lung tumorigenesis, and that the type of mutations produced by exposure to chemical carcinogens can influence the carcinogenic potential of the tumor. This may have prognostic significance in determining the malignant progression of the neoplasm.      

Immunological factors in milk from Brazilian mothers delivering small-for-date term neonates

Breast milk samples from three groups of Brazilian women were evaluated: G1, mothers delivering term babies of low birth weight (n=16); G2, mothers delivering preterm babies of appropriate birth weight (n = 20); G3, mothers delivering term babies of appropriate birth weight ( n = 30). Milk samples were obtained at 48 h and on the 7th, 15th, 30th and 60th days after delivery and they were analyzed for lysozyme and total IgA levels and for the presence of specific antibodies against Poliovirus types I, II, III, Rotavirus, Herpes simplex virus, Varicella zoster and Cytomegalovirus. The groups were not statistically different in relation to mother's age, parity, type of delivery or socio-economic levels. IgA levels were higher in both low-birth-weight groups (G1 & G2) compared to the control group (G3) throughout the study period. Lysozyme levels decreased up to the 15th day, increasing thereafter up to the 60th day in all groups. Specific antibodies were detected throughout the study period, with no differences among groups. We conclude that breast milk composition of mothers delivering low-birth-weight babies (G1 & G2) was similar despite the different gestational ages.     

Metastatic Intracranial Chordoma in a Child with Massive Pulmonary Tumor Emboli

A 27-month-old boy of Hispanic background developed multiple cranial nerve palsies, difficulty swallowing, bloody nasal discharge, and irritability. Radiographic evaluations showed extensive destruction of the clivus by a large tumor that invaded the sphenoid bone, left cavernous sinus, ethmoid sinus, nasal cavity, and left orbit. Multiple pulmonary nodules were also noted. The bone marrow and spinal fluid showed no evident tumor cells. Transnasal biopsy revealed a chordoma. Treatment was initiated with a combination of ifosfamide, mesna, and etoposide along with radiation therapy to the cranial tumor. Shifting pulmonary densities were noted on serial films. Despite some clinical improvement, the child developed rapidly progressive hypoxemia 3 weeks after admission and died. Autopsy showed persistent viable tumor in the primary site and massive pulmonary arteriolar tumor emboli, infarcts, and widespread lung parenchymal metastases. No other sites of tumor involvement were discovered. This is the second child reported with intracranial chordoma, pulmonary metastases at diagnosis, and early death attributed to pulmonary tumor emboli.     

Early pregnancy complications: endovaginal sonographic findings correlated with human chorionic gonadotropin levels

Endovaginal sonography results were compared with quantitatively determined human chorionic gonadotropin (hCG) levels in 84 women referred for early pregnancy complications. Of the 27 with normal intrauterine pregnancies, an intrauterine gestational sac was prospectively identified in one of five cases (20%) in which hCG levels were below 500 IU/L (Second International Standard), four of five (80%) with hCG levels of 500-1,000 IU/L, and all 17 with hCG levels above 1,000 IU/L. In comparison, 17 of the 26 women with ectopic pregnancies (65%) had hCG levels greater than 1,000 IU/L, and none of the 26 had an intrauterine gestational sac. Endovaginal sonography demonstrated an adnexal mass and/or a gestational sac-like structure in 16 of the 17 cases (94%) in which hCG levels were above 1,000 IU/L, compared with only three of the nine (33%) with lower hCG levels (P less than .01). These findings indicate that an intrauterine gestational sac should be normally visualized with endovaginal sonography when the hCG level exceeds 1,000 IU/L, and that visualization of an extrauterine gestational sac and/or adnexal mass is significantly more likely in ectopic pregnancies when the hCG level exceeds 1,000 IU/L.     

Childhood lymphoblastic cancer: subgroups defined by nonhuman primate antisera to human lymphatic leukemia cell antigens.

Lymphoblasts from 23 children with acute lymphocytic leukemia (ALL) and 10 with lymphoblastic lymphoma (LBL) were studied by complement-dependent microcytoxicity tests with two nonhuman primate antisera defining leukemia-associated and lymphoma-associated antigens. Cells form 15 patients with ALL and 1 with LBL reacted only with antiserum to chronic lymphatic leukemia (CLL). These group-I patients were predominantly female. Most were pancytopenic and lacked mediastinal widening and T-cell markers; lymphoblasts from 15 were periodic acid-Schiff-positive. Cells from 8 male patients reacted only with antiserum to converted lymphosarcoma (LS). All these group-II patients expressed T-cell markers; 5 had mediastinal enlargement and 2, an abdominal mass. Six of the 8 were PAS-negative. Cells from 9 patients reacted with both antisera. The group-III patients demonstrated some characteristics of each of the above groups. Patients whose lymphoblasts reacted with CLL antiserum presented with clinical and laboratory features indicative of a good prognosis, i.e., ALL with PAS positivity and no T-cell markers or localized mass. Patients whose cells reacted with LS antiserum often had bad prognostic features: mediastinal or abdominal mass, expression of T-cell markers, and PAS negativity. These antisera appear able to differentiate childhood ALL from LBL. The distinction is important prognostically and perhaps therapeutically.     

Extrapulmonary Tuberculosis in Human Immunodificiency Virus Infection

Background

In view of increase in incidence of exptrapulmonary tuberculosis after the epidemic of human immunodeficiency virus infection, the clinical profile of extrapulmonary tuberculosis in patients with HIV infection was studied.

Method

The study population comprised patients of HIV infection with extrapulmonary tuberculosis. Work up included history, clinical examination, sputum for acid fast bacilli, chext X-ray, ultrasonography (USG) abdomen, fine needle aspiration cytology(FNAC), transbronchial needle aspiration (TBNA) and computed tomography of chest.

Results

There were 50 cases, all males with mean age of 35 years. 24(48%) were without pulmonary tuberculosis and 26(52%) had pulmonary tuberculosis. 41(82%) had disseminated disease and 9(18%) involve one site. Fever and weight loss were the most frequent symptoms (79% and 58% respectively) in cases without pulmonary tuberculosis. The most frequent extrapulmonary site was lymph node in 46(92%), followed by spleen in 13(26%), pleura 9(18%), miliary 7(14%) and hepatic 1(2%). The diagnosis was confirmed by invasive methods in 30 out of 50(60%) cases [FNAC in 23(88%), TBNA in 2(25%) and pleural biopsy in 5(55%)].

Conclusion

In HIV infected patients, the most common extrapulmonary site is lymph mode followed by spleen.Key Words: Extrapulmonary TB, HIV Infection