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K Welch

Publications and source records attributed to K Welch.

At least 19 recordsLinked to original sources

Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line.

In this report we describe the identification and characterization of a novel tumor-associated receptor-type tyrosine kinase (hek). We produced a monoclonal antibody (III.A4) that detected a novel glycoprotein on the immunizing pre-B cell acute lymphoblastic leukemia cell line (LK63). This antigen was shown to be expressed sporadically on hemopoietic tumor cell lines and on ex vivo tumors. However, using antibody staining, the molecule was undetectable on normal tissues. Further biochemical characterization showed this molecule (hek) to be a phosphoroprotein. This observation taken together with the tumor-associated nature of hek expression suggested that hek might be a receptor-type protein tyrosine kinase. This was demonstrated by affinity purification of hek. In in vitro kinase experiments the purified hek protein was autophosphorylated on tyrosine and also mediated tyrosine phosphorylation of casein. Purified hek was subjected to N-terminal amino acid sequence analysis which showed that hek had a unique N terminus. Amino acid sequence determination of peptides from a V8 protease digest of hek yielded one 21-amino acid stretch of sequence which showed close homology with the eph subfamily of protein tyrosine kinases. These studies show hek to be a novel human tumor-associated protein tyrosine kinase, which by analogy with previously characterized protein tyrosine kinase proto-oncogenes, may have a role in tumorigenesis.

Amino Acid Sequence

Temporal lobectomy for complex partial seizures that began in childhood.

Forty-six consecutive patients who underwent surgery for intractable temporal lobe seizures originating in childhood are reported; invasive preoperative monitoring (e.g., depth electrodes and subdural arrays) was not used in the selection process. Our results, with respect to the control of seizures and improvement in behavior, are comparable to those of series in which invasive monitoring was used in the selection process. Eighty-five percent of the 46 patients (96% of the 28 operated after the introduction of long-term electroencephalographic monitoring) became either seizure free or experienced near total control of their seizures. Our results indicate that many patients can be selected successfully for temporal resection without exposure to the risk and expense of invasive presurgical procedures. A long duration of epilepsy prior to surgery in patients with neoplasia portended a less satisfactory outcome. Our results strengthen the argument for early operation in children with intractable epilepsy.

Adaptation, Psychological

Sumatriptan.

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History, 20th Century

Prevalence of tumor prevention rather than tumor enhancement when repetitive UV radiation treatments precede initiation and promotion.

UV irradiation can act as a tumor initiator in mouse skin, yet repetitive UV irradiation can systemically prevent chemically induced two-stage skin tumorigenesis. The present study addressed the question of whether repetitive dorsal UV irradiation would enhance or inhibit subsequent initiation and promotion applied dorsally. Approximately 4.25 x 10(5) J/m2 was applied intermittently to 30 shaved CDF1 mice over an 8 week period. Mice were then initiated dorsally with 100 micrograms of 7,12-dimethylbenz[a]anthracene and subsequently promoted with 7.5 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) applied twice weekly for 19 weeks. Initiated and promoted mice that had been treated repetitively with 1.06 x 10(4) J/m2 showed a decrease in tumor incidence from 92 to 28%, and a reduction in tumor yield per mouse from 5.35 to 0.58, at 19 weeks after the first TPA treatment. Histological analysis revealed that the UVB radiation treatments used in these experiments did not produce permanent loss of epidermal cells or sebaceous gland atrophy. When the same dose of UVB irradiation was applied after initiation and promotion, no increased conversion of papillomas to carcinomas was found, within a 48 weeks experimental duration. Thus, repetitive UV irradiation prevented rather than enhanced subsequent two-stage tumorigenesis. Repetitive UVB irradiation at late stages of promotion failed to enhance conversion of papillomas to carcinomas within the time frame in which chemical initiators mediate conversion to malignancy.

9,10-Dimethyl-1,2-benzanthracene

Cerebral hemicorticectomy for epilepsy.

Hemicorticectomy resulted in total or near-total control of seizures in 10 of 11 children with chronic epilepsy. During a median follow-up period of 5.5 years, there have been no deaths or delayed complications. The surgical outcome after hemicorticectomy compares favorably with that of more extensive surgical procedures, yet is associated with significantly less risk. The technique for hemicorticectomy is described and illustrated.

Adolescent

Results of surgery for extratemporal partial epilepsy that began in childhood.

Thirty-five consecutive patients who underwent surgery for intractable extratemporal seizures originating in childhood are described. Candidates for surgery were selected on the basis of clinical criteria, neurodiagnostic imaging, and an electroencephalographic investigation that included the use of sphenoidal electrodes and long-term monitoring. Invasive preoperative monitoring was not used. Our results, with respect to the control of seizures and behavioral improvement, are comparable with series in which data from invasive recordings were used in the selection process. Sixty-three percent of the 35 patients (76.5% of those operated on after the introduction of long-term electroencephalographic monitoring) became either seizure free or experienced a reduction in their frequency of seizures by at least 75%. The favorable outcome in this group of patients strengthens the argument for early operation in children with intractable epilepsy, even when the seizure focus is outside the temporal lobe.

Adolescent

Craniopharyngiomas in children. Long-term effects of conservative surgical procedures combined with radiation therapy.

Thirty-seven patients with craniopharyngioma were treated at Children's Hospital, Boston, between 1972 and 1981, the mean follow-up period now being 10.5 years. Twenty of these patients are old enough to have finished high school and have been queried about their college or job activity. None of the four patients who had undergone radical excision of their tumor and who had reached the age of finishing high school was able to work independently. Among the 16 patients who reached this age and who were treated by more conservative operations and irradiation or irradiation alone, job performance or college attendance varied considerably, indicating that psychosocial impairment occurred in this group, but suggesting that the risk was less. The rate of tumor recurrence or of failure to respond to treatment was 57% (four of a total of seven survivors) following radical surgery and 7% (two of 27 survivors) after conservative operations and irradiation. The overall mortality rate was 8%; the causes of the three deaths were: "hypothalamic crisis" 1 year after radical resection; progressive tumor growth despite two attempts at resection and irradiation; and a brain-stem glioma in the field of irradiation 8 years after treatment.

Child

Cloned stromal cell lines derived from human Whitlock/Witte-type long-term bone marrow cultures.

We report a human bone marrow culture technique that initially parallels the murine Whitlock/Witte culture system. As in the murine system, B cells predominate over other cell types, and all differentiation stages from pre-B to plasma cell are observed. Although these human long-term cultures pass through stages resembling phases I to III of murine Whitlock/Witte cultures, no outgrowth of nonadherent cells was seen after cultures had reached the "crisis" phase unless Epstein-Barr virus (EBV)-transformants appeared. The stromal cells persisted well beyond crisis, but they could not be maintained and passaged as cell lines, limiting their use in molecular analysis. Transfection of these stromal cells with plasmid DNA containing the simian virus 40 (SV40) early region yielded 124 cloned cell lines. Analysis of these lines showed that all expressed SV40 large T antigen, but they retained most phenotypic markers found on non-transformed stromal cells. When adherent and T-cell-depleted bone marrow cells were cultured on either nontransformed stromal layers or transformed cell lines they proliferated actively and soon yielded predominantly lymphoid nonadherent populations. Moreover, prolonged survival of acute lymphoblastic leukemia cells of pre-B phenotype was regularly achieved on both normal and transformed adherent cell layers. Although the liquid culture system favored lymphocytes, transformed stroma supported colony formation by both human and murine hemopoietic progenitors when marrow was added in agar medium. This was not explained by colony-stimulating factor (CSF) production, because striking heterogeneity in the levels of granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) secretion by the lines was noted. Some lines that did not produce detectable CSF demonstrated good support of fresh bone marrow growth and acute lymphoblastic leukemia (ALL) cell survival. The heterogeneity of these cell lines and their capacity to support hemopoiesis suggest that they will be useful in studying the molecular basis of in vitro lymphohemopoiesis in man.

Age Factors

Cognitive and social-emotional development of children in different preschool environments.

62 English-speaking preschool children were divided into three groups, a Montessori group (n = 21), a traditional preschool group (n = 21), and a homestaying group (n = 20) to compare their relative cognitive and social-emotional development. Significant differences in favour of the school groups were found for vocabulary, language comprehension, ability to judge the correctness of figural stimuli, visual memory, and perceptual organization. No differences were found for social-emotional development, and no relationship existed between type of preschool and level of development.

Child

The effect of furosemide on intracranial pressure and hemorrhage in preterm rabbits.

The hypothesis that intracranial hypotension due to excessive postnatal fluid loss places the premature infant at risk for germinal matrix and intraventricular hemorrhage (GM-IVH) was tested in preterm rabbits delivered at 28 and 29 days of gestation (term 32 days). Furosemide administered to newborn pups induced a diuresis that resulted in a 11% to 22% loss in body weight and a concomitant decline in muscle water (13% to 16%) and sodium (18% to 21%). Paradoxically, no change occurred in the water or electrolyte content of the brain even though cerebrospinal fluid and brain tissue pressure, but not blood pressure, declined. These changes were absent in littermates treated with saline. Microscopic examination of brain sections revealed a greater incidence of intracranial hemorrhage, particularly in the germinal matrix and choroid plexus, in furosemide-treated than in saline-treated preterm rabbit pups. These results are consistent with the hypothesis that intracranial hypotension promotes the incidence of GH-IVH in preterm animals.

Animals

Routine culture of stool specimens for Yersinia enterocolitica is not a cost-effective procedure.

Cefsulodin-Irgasin-novobiocin (CIN) agar was used to isolate Yersinia enterocolitica from 3,622 stool specimens received in our laboratory during a 1-year period. Seven specimens (0.2%) yielded Y. enterocolitica strains from a total of five patients. The low frequency of Y. enterocolitica isolation observed, coupled with the isolation of this pathogen from three of the five patients by our standard stool examination protocol, leads us to conclude that routine culture of stool specimens on CIN agar is not a cost-effective procedure.

Cost-Benefit Analysis

Residual shunt infection in a program aimed at its prevention.

Measures designed to prevent infection after cerebrospinal fluid shunts were described earlier. These include refinements in technique, postponement of operations when there is an actual or threatened leak of cerebrospinal fluid and the use of topical, systemic and intraventricular antibiotics. Six hundred and twenty-four operations in 404 patients, carried out after instituting these precautions were complicated by 13 new infections (2.1%) while in 5 instances (.8%) infection complicated a procedure conducted in the presence of a pre-existant but unrecognized infection. In almost every case the pathogenesis of new infection was clear. The circumstances suggest that some of the residual infections, both new and renewed, might by preventable.

Anti-Bacterial Agents